Aspirin / acetylsalicylic acid

duration

1 week of pre-treatment

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat

exposure

Aspirin 30 mg/kg

limitations

The comparator arm. Equivalence of endpoint at these two doses is not equivalence of mechanism, of potency per milligram, or of bleeding risk.

organism

Rat

plain_language

Aspirin at 30 mg/kg fully prevented occlusion in the same model, as the 500 mg/kg nattokinase dose did.

primary_references

Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. (2013) https://pubmed.ncbi.nlm.nih.gov/24396387/ DOI: 10.5625/lar.2013.29.4.221

route

In vivo, oral

tissue

Carotid artery, 35% FeCl3 injury, laser Doppler flow

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 312–312

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Rat · source_derived_draft · unverified_draft

Aspirin at 30 mg/kg fully prevented occlusion in the same model, as the 500 mg/kg nattokinase dose did.

duration

12 months

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human (1,062 outpatients)

exposure

Nattokinase with vitamin K2 and aspirin

limitations

A subgroup comparison inside an uncontrolled retrospective study by manufacturer-employed authors, with no formal interaction design. It points the opposite way from the case report in which nattokinase with aspirin preceded a cerebellar hemorrhage, and neither can settle the other.

organism

Human (1,062 outpatients)

plain_language

Co-administration of vitamin K2 and aspirin with nattokinase produced what the authors described as a synergistic effect on the same outcomes.

primary_references

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants. (2022) https://pubmed.ncbi.nlm.nih.gov/36072877/ DOI: 10.3389/fcvm.2022.964977 Correction on record: Erratum in: Front Cardiovasc Med. 2022 Dec 05;9:1076420. doi: 10.3389/fcvm.2022.1076420. PMID 36545015.

route

In vivo, oral

tissue

Carotid artery imaging and blood lipids

Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 1170–1170

Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Human (1,062 outpatients) · source_derived_draft · unverified_draft

Co-administration of vitamin K2 and aspirin with nattokinase produced what the authors described as a synergistic effect on the same outcomes.

dose

Aspirin 150 mg/kg body weight for 3 weeks, starting one week before tartrazine 700 mg/kg for 2 weeks

duration

3 weeks total; 2 weeks co-exposure

evidence_access

Primary full-text methods/results and metadata.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

Male Wistar rats; six per group

limitations

High-dose preclinical experiment, not an aspirin treatment recommendation. The routes differ and the study does not establish antioxidant or p53 mediation.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

Male Wistar rats; six per group

plain_language

Aspirin pretreatment and co-exposure attenuated the brain histological injury observed with high-dose tartrazine.

primary_references

High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain. (2019). https://pubmed.ncbi.nlm.nih.gov/31032366/ DOI: 10.1155/2019/9096404

route

Intraperitoneal aspirin plus oral tartrazine

tissue

Brain histopathology

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 391–400

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Male Wistar rats; six per group · source_derived_draft · unverified_draft

## tartrazine-aspirin-histology Aspirin pretreatment and co-exposure attenuated the brain histological injury observed with high-dose tartrazine. Model/species: Male Wistar rats; six per group Tissue: Brain histopathology Exposure: Aspirin 150 mg/kg body weight for 3 weeks, starting one week before tartrazine 700 mg/kg for 2 weeks Route: Intraperitoneal aspirin plus oral tartrazine Duration: 3 weeks total; 2 weeks co-exposure Limits: High-dose preclinical experiment, not an aspirin treatment recommendation. The routes differ and the study does not establish antioxidant or p53 mediation. Primary reference: High-Dose Aspirin Reverses Tartrazine-Induced Cell Growth Dysregulation Independent of p53 Signaling and Antioxidant Mechanisms in Rat Brain. (2019). https://pubmed.ncbi.nlm.nih.gov/31032366/ DOI: 10.1155/2019/9096404 Access: Primary full-text methods/results and metadata.

evidence_span

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experimental_model

Human and rabbit platelet aggregation with rabbit aortic prostacyclin synthesis measured across aspirin doses

exposure

Graded oral aspirin doses, sampled three hours after dosing, with recovery followed over 24 hours in rabbits

limitations

Sets the dose at which the two tissues start to separate, but the vascular arm is rabbit aorta and the human arm measures aggregation rather than prostacyclin.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human and rabbit

plain_language

About a quarter of a tablet stops the platelets while mostly leaving the vessel wall alone.

primary_references

[asa-p6156337] Effect of oral aspirin dose on platelet aggregation and vascular prostacyclin (PGI2) synthesis in humans and rabbits. (1980). https://pubmed.ncbi.nlm.nih.gov/6156337/ DOI: 10.1097/00005344-198007000-00006

tissue_or_cell_type

Platelets and aorta

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 390–401

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and rabbit platelet aggregation with rabbit aortic prostacyclin synthesis measured across aspirin doses · source_derived_draft · unverified_draft

### asa-a-quarter-tablet In rabbits lower doses of aspirin produced major inhibition of platelet aggregation and minor inhibition of prostacyclin synthesis while higher doses inhibited both, in humans a dose equivalent to approximately one quarter of one 300 milligram tablet consistently produced major inhibition of cyclooxygenase-dependent platelet aggregation in a pattern similar to that in rabbits where most prostacyclin synthetic capacity was not inhibited, and it took rabbit vasculature over 24 hours to return to control prostacyclin synthetic capacity after a single high dose. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: About a quarter of a tablet stops the platelets while mostly leaving the vessel wall alone. organism: Human and rabbit tissue_or_cell_type: Platelets and aorta experimental_model: Human and rabbit platelet aggregation with rabbit aortic prostacyclin synthesis measured across aspirin doses limitations: Sets the dose at which the two tissues start to separate, but the vascular arm is rabbit aorta and the human arm measures aggregation rather than prostacyclin. exposure: Graded oral aspirin doses, sampled three hours after dosing, with recovery followed over 24 hours in rabbits evidence_span: {"source_cache": "artifacts/aspirin-research/6156337.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0d904fae5d8c006bd180213b6b2cbc88c87bb103b9c8b8872705330c349b074", "start_char": 0, "end_char": 1502, "text_sha256": "e0d904fae5d8c006bd180213b6b2cbc88c87bb103b9c8b8872705330c349b074"} [asa-p6156337] Effect of oral aspirin dose on platelet aggregation and vascular prostacyclin (PGI2) synthesis in humans and rabbits. (1980). https://pubmed.ncbi.nlm.nih.gov/6156337/ DOI: 10.1097/00005344-198007000-00006

evidence_span

{"source_cache": "artifacts/aspirin-research/9660772.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259", "start_char": 0, "end_char": 1662, "text_sha256": "49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259"}

experimental_model

Inhibition and acetylation of plant allene oxide synthase, a cytochrome P450

exposure

Aspirin and salicylic acid applied to the plant oxylipin pathway

limitations

Recorded because it shows the acetyl group is not specific to cyclooxygenase. The three acetylated serines here are not thought to line the substrate channel, so the mechanism may differ from the one at cyclooxygenase.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Plant

plain_language

Aspirin hands its acetyl group to other enzymes too, including one in plants, and not always at the substrate channel.

primary_references

[asa-p9660772] Aspirin inhibition and acetylation of the plant cytochrome P450, allene oxide synthase, resembles that of animal prostaglandin endoperoxide H synthase. (1998). https://pubmed.ncbi.nlm.nih.gov/9660772/ DOI: 10.1074/jbc.273.29.18139

tissue_or_cell_type

Allene oxide synthase

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 195–206

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibition and acetylation of plant allene oxide synthase, a cytochrome P450 · source_derived_draft · unverified_draft

### asa-acetylates-other-enzymes Aspirin causes time-dependent inhibition and acetylation of plant allene oxide synthase leading to irreversible inactivation of this cytochrome P450, acetylating three serine residues near the C-terminal region that are highly conserved among allene oxide synthases but not among classical P450s; unlike animal cyclooxygenase, where acetylation of a single serine within the substrate channel causes inactivation, these three serines are not thought to line the putative substrate channel, so inhibition may be by a different mechanism, and aspirin could inhibit other P450s with similar motifs. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Aspirin hands its acetyl group to other enzymes too, including one in plants, and not always at the substrate channel. organism: Plant tissue_or_cell_type: Allene oxide synthase experimental_model: Inhibition and acetylation of plant allene oxide synthase, a cytochrome P450 limitations: Recorded because it shows the acetyl group is not specific to cyclooxygenase. The three acetylated serines here are not thought to line the substrate channel, so the mechanism may differ from the one at cyclooxygenase. exposure: Aspirin and salicylic acid applied to the plant oxylipin pathway evidence_span: {"source_cache": "artifacts/aspirin-research/9660772.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259", "start_char": 0, "end_char": 1662, "text_sha256": "49e5d050a7b1505f537ae535df4e7a51563a72d528973779baf53c963b50c259"} [asa-p9660772] Aspirin inhibition and acetylation of the plant cytochrome P450, allene oxide synthase, resembles that of animal prostaglandin endoperoxide H synthase. (1998). https://pubmed.ncbi.nlm.nih.gov/9660772/ DOI: 10.1074/jbc.273.29.18139

evidence_span

{"source_cache": "artifacts/aspirin-research/2108169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50", "start_char": 0, "end_char": 2076, "text_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50"}

experimental_model

Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells

exposure

Serine 530 replaced with alanine, compared with the native enzyme against aspirin and reversible inhibitors

limitations

The decisive experiment for the mechanism: it separates what the serine does for catalysis from what acetylating it does. Recombinant sheep enzyme, not human enzyme in a tissue.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Sheep and mouse enzyme

plain_language

The acetyl group works by being in the way, not by removing something the enzyme needed.

primary_references

[asa-p2108169] The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2108169/ DOI: 10.1016/s0021-9258(19)34105-5

tissue_or_cell_type

Recombinant enzyme in Cos-1 cells

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 91–102

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells · source_derived_draft · unverified_draft

### asa-acetylation-is-steric Acetylation of Ser-530 of sheep prostaglandin endoperoxide synthase by aspirin causes irreversible inactivation of the cyclooxygenase activity of the enzyme, and since the serine hydroxyl is not required for catalysis the acetylation apparently introduces a bulky side chain at position 530 which interferes with arachidonate binding; a sequence of 35 residues with Ser-530 at the midpoint was identical in the sheep and mouse enzymes. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The acetyl group works by being in the way, not by removing something the enzyme needed. organism: Sheep and mouse enzyme tissue_or_cell_type: Recombinant enzyme in Cos-1 cells experimental_model: Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells limitations: The decisive experiment for the mechanism: it separates what the serine does for catalysis from what acetylating it does. Recombinant sheep enzyme, not human enzyme in a tissue. exposure: Serine 530 replaced with alanine, compared with the native enzyme against aspirin and reversible inhibitors evidence_span: {"source_cache": "artifacts/aspirin-research/2108169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50", "start_char": 0, "end_char": 2076, "text_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50"} [asa-p2108169] The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2108169/ DOI: 10.1016/s0021-9258(19)34105-5

evidence_span

{"source_cache": "artifacts/aspirin-research/7568157.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d9e7b80265068fb60f67e97c9d46de7a25e0099151b6d7fbc688f70a29ee9b9b", "start_char": 0, "end_char": 2036, "text_sha256": "d9e7b80265068fb60f67e97c9d46de7a25e0099151b6d7fbc688f70a29ee9b9b"}

experimental_model

Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products

exposure

Aspirin compared against indomethacin, salicylate and dexamethasone, with interleukin-1-beta induction and several costimuli

limitations

The comparator set is what makes this strong: three other anti-inflammatory drugs including salicylate failed to produce the same products. It is a cell coincubation, and the nanomolar activity is measured on adhesion in vitro.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human cells

plain_language

Aspirin, and not the other anti-inflammatories tested, makes the body build a mediator it otherwise never makes.

primary_references

[asa-p7568157] Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. (1995). https://pubmed.ncbi.nlm.nih.gov/7568157/ DOI: 10.1073/pnas.92.21.9475

tissue_or_cell_type

Endothelium and neutrophils

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 312–323

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products · source_derived_draft · unverified_draft

### asa-aspirin-triggers-lipoxins Aspirin triggered transcellular biosynthesis of a previously unrecognised class of eicosanoids during coincubations of human umbilical vein endothelial cells and neutrophils, generated with aspirin but not by indomethacin, salicylate or dexamethasone, enhanced by interleukin-1-beta which induced cyclooxygenase-2 but not 15-lipoxygenase; four products proved to be 15R-epimers of lipoxins, two were potent inhibitors of leukotriene B4-mediated neutrophil adhesion to endothelium, with 15-epi-lipoxin A4 active in the nanomolar range, an example of a drug pirating endogenous biosynthetic mechanisms to trigger new mediators. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Aspirin, and not the other anti-inflammatories tested, makes the body build a mediator it otherwise never makes. organism: Human cells tissue_or_cell_type: Endothelium and neutrophils experimental_model: Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products limitations: The comparator set is what makes this strong: three other anti-inflammatory drugs including salicylate failed to produce the same products. It is a cell coincubation, and the nanomolar activity is measured on adhesion in vitro. exposure: Aspirin compared against indomethacin, salicylate and dexamethasone, with interleukin-1-beta induction and several costimuli evidence_span: {"source_cache": "artifacts/aspirin-research/7568157.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d9e7b80265068fb60f67e97c9d46de7a25e0099151b6d7fbc688f70a29ee9b9b", "start_char": 0, "end_char": 2036, "text_sha256": "d9e7b80265068fb60f67e97c9d46de7a25e0099151b6d7fbc688f70a29ee9b9b"} [asa-p7568157] Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. (1995). https://pubmed.ncbi.nlm.nih.gov/7568157/ DOI: 10.1073/pnas.92.21.9475

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/aspirin-research/23094721.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fab66fe6fa87b7288d31cfbda54b13b3a1d81fd32302054aa4c791b9d6ede43", "start_char": 0, "end_char": 2456, "text_sha256": "0fab66fe6fa87b7288d31cfbda54b13b3a1d81fd32302054aa4c791b9d6ede43"}

experimental_model

Molecular pathological epidemiology in 964 colorectal cancer patients from the Nurses’ Health Study and the Health Professionals Follow-up Study

exposure

Regular aspirin use after diagnosis, stratified by tumour PIK3CA mutation status

limitations

Observational cohorts with tumour genotyping, not a randomised trial, so aspirin use after diagnosis is chosen rather than assigned and may travel with other differences between patients.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

Aspirin after diagnosis tracked with much better survival, but only in tumours carrying one particular mutation.

primary_references

[asa-p23094721] Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. (2012). https://pubmed.ncbi.nlm.nih.gov/23094721/ DOI: 10.1056/nejmoa1207756

tissue_or_cell_type

Colorectal tumour

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 598–609

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Molecular pathological epidemiology in 964 colorectal cancer patients from the Nurses’ Health Study and the Health Professionals Follow-up Study · source_derived_draft · unverified_draft

### asa-benefit-tracks-pik3ca Among 964 colorectal cancer patients, regular aspirin use after diagnosis was associated with superior colorectal-cancer-specific survival in those with mutated-PIK3CA cancers, multivariate hazard ratio for cancer-related death 0.18 with 95% confidence interval 0.06 to 0.61, and superior overall survival at hazard ratio 0.54, whereas among patients with wild-type PIK3CA there was no association with cancer-specific survival at hazard ratio 0.96 or overall survival at 0.94, with the interaction between aspirin and PIK3CA yielding a p value of 0.009. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Aspirin after diagnosis tracked with much better survival, but only in tumours carrying one particular mutation. organism: Human tissue_or_cell_type: Colorectal tumour experimental_model: Molecular pathological epidemiology in 964 colorectal cancer patients from the Nurses’ Health Study and the Health Professionals Follow-up Study limitations: Observational cohorts with tumour genotyping, not a randomised trial, so aspirin use after diagnosis is chosen rather than assigned and may travel with other differences between patients. exposure: Regular aspirin use after diagnosis, stratified by tumour PIK3CA mutation status evidence_span: {"source_cache": "artifacts/aspirin-research/23094721.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0fab66fe6fa87b7288d31cfbda54b13b3a1d81fd32302054aa4c791b9d6ede43", "start_char": 0, "end_char": 2456, "text_sha256": "0fab66fe6fa87b7288d31cfbda54b13b3a1d81fd32302054aa4c791b9d6ede43"} [asa-p23094721] Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. (2012). https://pubmed.ncbi.nlm.nih.gov/23094721/ DOI: 10.1056/nejmoa1207756

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/aspirin-research/7045161.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "58bb82650f675f1ba3dd21b6dcf3d83b71a56c437a687f72d2af9dcdc07abadb", "start_char": 0, "end_char": 1963, "text_sha256": "58bb82650f675f1ba3dd21b6dcf3d83b71a56c437a687f72d2af9dcdc07abadb"}

experimental_model

Radioimmunoassay of serum thromboxane B2 and urinary prostaglandin excretion in 46 healthy subjects given single or repeated oral aspirin

exposure

Single doses of 6 to 100 milligrams, and 0.45 milligrams per kilogram daily for 7 days and up to one month

limitations

The dose-ranging design across 46 subjects is what makes the selectivity claim testable. Urinary prostaglandin excretion is an indirect measure of renal synthesis.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

A very small daily dose wipes out platelet thromboxane and leaves the kidney untouched.

primary_references

[asa-p7045161] Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. (1982). https://pubmed.ncbi.nlm.nih.gov/7045161/ DOI: 10.1172/jci110576

tissue_or_cell_type

Platelets and kidney

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 364–375

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radioimmunoassay of serum thromboxane B2 and urinary prostaglandin excretion in 46 healthy subjects given single or repeated oral aspirin · source_derived_draft · unverified_draft

### asa-cumulative-and-selective Single doses of 6 to 100 milligrams of aspirin produced a linear inhibition of platelet thromboxane B2 production ranging from 12 to 95% after 24 hours, and a daily dose of 0.45 milligrams per kilogram for 7 days produced cumulative and virtually complete inhibition without significantly reducing urinary excretion of prostaglandin E2, prostaglandin F2-alpha or 6-keto-prostaglandin F1-alpha in both men and women, an effect maintained unaltered through one month of therapy with no cumulative inhibition of renal prostaglandin synthesis, while furosemide-induced renal prostacyclin synthesis and renin release were unaffected. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: A very small daily dose wipes out platelet thromboxane and leaves the kidney untouched. organism: Human tissue_or_cell_type: Platelets and kidney experimental_model: Radioimmunoassay of serum thromboxane B2 and urinary prostaglandin excretion in 46 healthy subjects given single or repeated oral aspirin limitations: The dose-ranging design across 46 subjects is what makes the selectivity claim testable. Urinary prostaglandin excretion is an indirect measure of renal synthesis. exposure: Single doses of 6 to 100 milligrams, and 0.45 milligrams per kilogram daily for 7 days and up to one month evidence_span: {"source_cache": "artifacts/aspirin-research/7045161.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "58bb82650f675f1ba3dd21b6dcf3d83b71a56c437a687f72d2af9dcdc07abadb", "start_char": 0, "end_char": 1963, "text_sha256": "58bb82650f675f1ba3dd21b6dcf3d83b71a56c437a687f72d2af9dcdc07abadb"} [asa-p7045161] Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. (1982). https://pubmed.ncbi.nlm.nih.gov/7045161/ DOI: 10.1172/jci110576

evidence_span

{"source_cache": "artifacts/aspirin-research/7003384.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38", "start_char": 0, "end_char": 1148, "text_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38"}

experimental_model

Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites

exposure

150 or 300 milligrams of oral aspirin

limitations

Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

At ordinary tablet doses the vessel wall is hit about as hard as the platelet.

primary_references

[asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203

tissue_or_cell_type

Vein wall and platelets

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 377–388

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites · source_derived_draft · unverified_draft

### asa-no-selectivity-at-higher-dose Two hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: At ordinary tablet doses the vessel wall is hit about as hard as the platelet. organism: Human tissue_or_cell_type: Vein wall and platelets experimental_model: Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites limitations: Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold. exposure: 150 or 300 milligrams of oral aspirin evidence_span: {"source_cache": "artifacts/aspirin-research/7003384.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38", "start_char": 0, "end_char": 1148, "text_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38"} [asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203

evidence_span

{"source_cache": "artifacts/aspirin-research/7355437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a", "start_char": 0, "end_char": 909, "text_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a"}

experimental_model

High pressure liquid chromatography of plasma acetylsalicylate and salicylate with radiometric platelet cyclooxygenase assay

exposure

650 milligrams of aspirin as compressed or enteric-coated tablets

limitations

Measures the parent drug and the metabolite separately alongside the enzyme effect, which is exactly the distinction this chapter turns on. Healthy subjects and a single dose.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

The drug catches the platelets that are in the blood at the time, and nothing else.

primary_references

[asa-p7355437] Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin. (1980). https://pubmed.ncbi.nlm.nih.gov/7355437/ DOI: 10.1161/01.str.11.1.9

tissue_or_cell_type

Plasma and platelets

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 403–414

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High pressure liquid chromatography of plasma acetylsalicylate and salicylate with radiometric platelet cyclooxygenase assay · source_derived_draft · unverified_draft

### asa-only-circulating-platelets Following ingestion of 650 milligrams of acetylsalicylate as compressed tablets, platelet cyclooxygenase activity was inhibited 95% within 45 minutes, enzyme activity was observed to increase within 8 hours and reached 10% of control level by 24 hours, a pattern suggesting that only circulating platelets are affected by ingestion; enteric-coated tablets gave comparable inhibition with a delayed onset reflecting delayed appearance of acetylsalicylate in plasma, and returned to control along a similar pattern. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The drug catches the platelets that are in the blood at the time, and nothing else. organism: Human tissue_or_cell_type: Plasma and platelets experimental_model: High pressure liquid chromatography of plasma acetylsalicylate and salicylate with radiometric platelet cyclooxygenase assay limitations: Measures the parent drug and the metabolite separately alongside the enzyme effect, which is exactly the distinction this chapter turns on. Healthy subjects and a single dose. exposure: 650 milligrams of aspirin as compressed or enteric-coated tablets evidence_span: {"source_cache": "artifacts/aspirin-research/7355437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a", "start_char": 0, "end_char": 909, "text_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a"} [asa-p7355437] Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin. (1980). https://pubmed.ncbi.nlm.nih.gov/7355437/ DOI: 10.1161/01.str.11.1.9

evidence_span

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experimental_model

Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them

exposure

Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates

limitations

Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. It is an in vitro enzyme study, so it does not exclude accumulation or amplification in a living tissue.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human enzyme

plain_language

Aspirin only ever modifies half of the paired enzyme, and the untouched half carries on at a fifth speed.

primary_references

[asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115

tissue_or_cell_type

Cyclooxygenase-2 homodimer

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them · source_derived_draft · unverified_draft

### asa-only-one-monomer-is-acetylated Aspirin maximally acetylates one monomer of human cyclooxygenase-2, the acetylated monomer forming 15-hydroperoxyeicosatetraenoic acid from arachidonic acid while the nonacetylated partner monomer forms mainly prostaglandin H2 but at only 15 to 20% of the rate of native enzyme, conclusions based on diclofenac binding a single monomer of native enzyme having an unmodified Ser530 and on diclofenac inhibiting prostaglandin H2 but not 15-hydroperoxyeicosatetraenoic acid formation by the acetylated enzyme. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Aspirin only ever modifies half of the paired enzyme, and the untouched half carries on at a fifth speed. organism: Human enzyme tissue_or_cell_type: Cyclooxygenase-2 homodimer experimental_model: Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them limitations: Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. It is an in vitro enzyme study, so it does not exclude accumulation or amplification in a living tissue. exposure: Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates evidence_span: {"source_cache": "artifacts/aspirin-research/20194532.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf", "start_char": 0, "end_char": 1441, "text_sha256": "09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf"} [asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115

evidence_span

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experimental_model

Double-blind nasal lavage challenge in ten aspirin-sensitive asthmatics, ten insensitive asthmatics and seven healthy subjects

exposure

12 milligrams of acetylsalicylic acid instilled nasally against saline

limitations

Three groups including two control groups, with mediators measured directly in the target tissue. Radioimmunoassay of nasal lavage fluid, and a small number per group.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

The drug blocks prostaglandins in everyone, but only in the sensitive patients does a flood of leukotrienes follow.

primary_references

[asa-p1309968] Release of peptide leukotriene into nasal secretions after local instillation of aspirin in aspirin-sensitive asthmatic patients. (1992). https://pubmed.ncbi.nlm.nih.gov/1309968/ DOI: 10.1164/ajrccm/145.1.65

tissue_or_cell_type

Nasal mucosa

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 572–583

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind nasal lavage challenge in ten aspirin-sensitive asthmatics, ten insensitive asthmatics and seven healthy subjects · source_derived_draft · unverified_draft

### asa-only-sensitive-patients-release After nasal instillation of 12 milligrams of acetylsalicylic acid, significant levels of peptide leukotrienes were detected in sensitive asthmatic patients at 60 minutes in association with a significant increase in symptoms, with no increase in either insensitive patients or healthy subjects, while inhibition of prostaglandin E2 and F2-alpha release was detected in all three groups; aspirin also inhibited prostaglandin D2 release in insensitive asthmatic patients but not in sensitive patients or healthy subjects. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The drug blocks prostaglandins in everyone, but only in the sensitive patients does a flood of leukotrienes follow. organism: Human tissue_or_cell_type: Nasal mucosa experimental_model: Double-blind nasal lavage challenge in ten aspirin-sensitive asthmatics, ten insensitive asthmatics and seven healthy subjects limitations: Three groups including two control groups, with mediators measured directly in the target tissue. Radioimmunoassay of nasal lavage fluid, and a small number per group. exposure: 12 milligrams of acetylsalicylic acid instilled nasally against saline evidence_span: {"source_cache": "artifacts/aspirin-research/1309968.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81a9ed941df59e6b8aa8c7c730d9a14766e2b8bd358b712ee464ae96c67e4e2", "start_char": 0, "end_char": 1685, "text_sha256": "a81a9ed941df59e6b8aa8c7c730d9a14766e2b8bd358b712ee464ae96c67e4e2"} [asa-p1309968] Release of peptide leukotriene into nasal secretions after local instillation of aspirin in aspirin-sensitive asthmatic patients. (1992). https://pubmed.ncbi.nlm.nih.gov/1309968/ DOI: 10.1164/ajrccm/145.1.65

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

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experimental_model

Factorial study in young male ferrets made hyperammonaemic by brief arginine-deficient feeding

exposure

Influenza infection and aspirin treatment, alone and together, in control and hyperammonaemic animals

limitations

An animal model of a syndrome whose human definition is clinical, testing three factors that cannot be separated in patients because dosing precedes diagnosis. Synergism is reported across biochemical parameters rather than as a disease endpoint.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Ferret

plain_language

In this model aspirin only does damage alongside a viral infection and a failing urea cycle; no one factor is enough.

primary_references

[asa-p6961432] Interactions of aspirin and other potential etiologic factors in an animal model of Reye syndrome. (1982). https://pubmed.ncbi.nlm.nih.gov/6961432/ DOI: 10.1073/pnas.79.23.7557

tissue_or_cell_type

Liver and blood

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 585–596

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial study in young male ferrets made hyperammonaemic by brief arginine-deficient feeding · source_derived_draft · unverified_draft

### asa-reye-needs-three-factors In young male ferrets made hyperammonaemic and comatose by brief feeding of an arginine-deficient diet, synergism of the three factors hyperammonaemia, influenza infection and aspirin treatment was observed in causing Reye-syndrome-like alterations in serum ammonia, transaminase, ornithine carbamoyltransferase, bilirubin and salicylate levels and in liver lipids, proteins and urea-cycle enzymes; the relationship of aspirin treatment to influenza and ammonia toxicity cannot be examined directly in patients because aspirin is usually started by family members in the prodrome before the syndrome is diagnosed. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: In this model aspirin only does damage alongside a viral infection and a failing urea cycle; no one factor is enough. organism: Ferret tissue_or_cell_type: Liver and blood experimental_model: Factorial study in young male ferrets made hyperammonaemic by brief arginine-deficient feeding limitations: An animal model of a syndrome whose human definition is clinical, testing three factors that cannot be separated in patients because dosing precedes diagnosis. Synergism is reported across biochemical parameters rather than as a disease endpoint. exposure: Influenza infection and aspirin treatment, alone and together, in control and hyperammonaemic animals evidence_span: {"source_cache": "artifacts/aspirin-research/6961432.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53631b4bef8684ad8023f1dcc822f8191323e61fd073a93ce4c4872916cb5beb", "start_char": 0, "end_char": 1430, "text_sha256": "53631b4bef8684ad8023f1dcc822f8191323e61fd073a93ce4c4872916cb5beb"} [asa-p6961432] Interactions of aspirin and other potential etiologic factors in an animal model of Reye syndrome. (1982). https://pubmed.ncbi.nlm.nih.gov/6961432/ DOI: 10.1073/pnas.79.23.7557

evidence_span

{"source_cache": "artifacts/aspirin-research/8175750.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ba85af90c62b157cf53032375ca703e8b78eff6ddd22ad627bbd7e65965d8e9", "start_char": 0, "end_char": 1786, "text_sha256": "9ba85af90c62b157cf53032375ca703e8b78eff6ddd22ad627bbd7e65965d8e9"}

experimental_model

Human cyclooxygenase-1 and -2 expressed in cos-1 cells treated with aspirin and with carbon-14 labelled aspirin, with a mutant series at Ser-516

exposure

Aspirin acetylation, with S516A, S516N, S516Q and S516M substitutions

limitations

Identifies the site by direct labelling and explains the isoform difference by active site volume. Recombinant enzyme in a heterologous cell line.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human enzyme

plain_language

The labelled acetyl group lands on one serine, and the second enzyme’s pocket is roomier, which is why the two behave differently.

primary_references

[asa-p8175750] Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8175750/ DOI: 10.1016/s0021-9258(17)36820-5

tissue_or_cell_type

Recombinant cyclooxygenase

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 221–232

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cyclooxygenase-1 and -2 expressed in cos-1 cells treated with aspirin and with carbon-14 labelled aspirin, with a mutant series at Ser-516 · source_derived_draft · unverified_draft

### asa-ser516-is-the-site When microsomal human cyclooxygenase-2 was incubated with acetyl-carbon-14 labelled aspirin the enzyme was acetylated, while an S516A mutant which retains enzyme activity was not acetylated, indicating that Ser-516 is the site of aspirin acetylation and is homologous to the active site serine of cyclooxygenase-1; an S516N mutant was catalytically active whereas an S516Q mutant lacked cyclooxygenase but retained peroxidase activity, and because in cyclooxygenase-1 the smaller asparagine substitution suffices to eliminate cyclooxygenase activity the active site of cyclooxygenase-2 is slightly larger. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The labelled acetyl group lands on one serine, and the second enzyme’s pocket is roomier, which is why the two behave differently. organism: Human enzyme tissue_or_cell_type: Recombinant cyclooxygenase experimental_model: Human cyclooxygenase-1 and -2 expressed in cos-1 cells treated with aspirin and with carbon-14 labelled aspirin, with a mutant series at Ser-516 limitations: Identifies the site by direct labelling and explains the isoform difference by active site volume. Recombinant enzyme in a heterologous cell line. exposure: Aspirin acetylation, with S516A, S516N, S516Q and S516M substitutions evidence_span: {"source_cache": "artifacts/aspirin-research/8175750.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ba85af90c62b157cf53032375ca703e8b78eff6ddd22ad627bbd7e65965d8e9", "start_char": 0, "end_char": 1786, "text_sha256": "9ba85af90c62b157cf53032375ca703e8b78eff6ddd22ad627bbd7e65965d8e9"} [asa-p8175750] Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8175750/ DOI: 10.1016/s0021-9258(17)36820-5

evidence_span

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experimental_model

Review of arachidonate metabolism in airway hyperreactivity and aspirin-induced asthma

exposure

Cyclooxygenase inhibition and the proposed diversion of arachidonate into the lipoxygenase pathway

limitations

A review from 1981 setting out the shunting hypothesis. It is recorded as the proposal that later work tested, not as evidence that the proposal is right.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

The standard explanation: block one pathway and the raw material spills into another that makes bronchoconstrictors.

primary_references

[asa-p6113615] Lipoxygenase pathway and hydroperoxy acids: possible relevance to aspirin-induced asthma and hyperirritability of airways in asthmatics. (1981). https://pubmed.ncbi.nlm.nih.gov/6113615/ DOI: 10.1016/0161-4630(81)90097-5

tissue_or_cell_type

Airway

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 546–557

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of arachidonate metabolism in airway hyperreactivity and aspirin-induced asthma · source_derived_draft · unverified_draft

### asa-shunting-proposed The adverse effect of aspirin in asthmatics is often attributed to inhibition of the synthesis and release of defensive modulatory endogenous prostaglandins in the lungs, removing their negative feedback on allergic mediator release, and in addition work suggests diversion of arachidonic acid metabolism via the lipoxygenase pathway after cyclooxygenase inhibition, leading to formation of hydroperoxy acids and leukotrienes whose accumulation in sensitive individuals could explain the mechanism of aspirin-induced asthma. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The standard explanation: block one pathway and the raw material spills into another that makes bronchoconstrictors. organism: Human tissue_or_cell_type: Airway experimental_model: Review of arachidonate metabolism in airway hyperreactivity and aspirin-induced asthma limitations: A review from 1981 setting out the shunting hypothesis. It is recorded as the proposal that later work tested, not as evidence that the proposal is right. exposure: Cyclooxygenase inhibition and the proposed diversion of arachidonate into the lipoxygenase pathway evidence_span: {"source_cache": "artifacts/aspirin-research/6113615.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "184fc232146a3837f396109d951c9755155f181c524a3ffaa330645138d8a616", "start_char": 0, "end_char": 2083, "text_sha256": "184fc232146a3837f396109d951c9755155f181c524a3ffaa330645138d8a616"} [asa-p6113615] Lipoxygenase pathway and hydroperoxy acids: possible relevance to aspirin-induced asthma and hyperirritability of airways in asthmatics. (1981). https://pubmed.ncbi.nlm.nih.gov/6113615/ DOI: 10.1016/0161-4630(81)90097-5

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

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experimental_model

Platelet aggregation and cyclooxygenase activity in subjects given ibuprofen before aspirin, in vitro and in vivo

exposure

Ibuprofen ingestion followed by 650 milligrams of aspirin, with recovery followed to 26 hours

limitations

The observation is clean and has been confirmed since. The authors’ inference from it, that aspirin must act on the heme group rather than by acetylating the protein, is contradicted by the mutant and crystallographic records in this collection and is not adopted here.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

Take ibuprofen first and aspirin never gets its chance; the protection wears off in a day like ibuprofen, not like aspirin.

primary_references

[asa-p6411052] Ibuprofen protects platelet cyclooxygenase from irreversible inhibition by aspirin. (1983). https://pubmed.ncbi.nlm.nih.gov/6411052/ DOI: 10.1161/01.atv.3.4.383

tissue_or_cell_type

Platelets

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 442–453

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Platelet aggregation and cyclooxygenase activity in subjects given ibuprofen before aspirin, in vitro and in vivo · source_derived_draft · unverified_draft

### asa-ibuprofen-blocks-aspirin Platelet function and prostaglandin synthesis recovered completely 26 hours after ingestion of ibuprofen but remained compromised 26 hours after taking aspirin, and when 650 milligrams of aspirin was administered after ibuprofen, platelet function and cyclooxygenase activity recovered as completely at 26 hours as in platelets exposed to ibuprofen alone, so prior exposure to ibuprofen in vivo completely protected cyclooxygenase from the irreversible effects of aspirin. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Take ibuprofen first and aspirin never gets its chance; the protection wears off in a day like ibuprofen, not like aspirin. organism: Human tissue_or_cell_type: Platelets experimental_model: Platelet aggregation and cyclooxygenase activity in subjects given ibuprofen before aspirin, in vitro and in vivo limitations: The observation is clean and has been confirmed since. The authors’ inference from it, that aspirin must act on the heme group rather than by acetylating the protein, is contradicted by the mutant and crystallographic records in this collection and is not adopted here. exposure: Ibuprofen ingestion followed by 650 milligrams of aspirin, with recovery followed to 26 hours evidence_span: {"source_cache": "artifacts/aspirin-research/6411052.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a685344a88574182dbad6f8d70308dce88384a63ed0c561ccaec4d522000b132", "start_char": 0, "end_char": 1551, "text_sha256": "a685344a88574182dbad6f8d70308dce88384a63ed0c561ccaec4d522000b132"} [asa-p6411052] Ibuprofen protects platelet cyclooxygenase from irreversible inhibition by aspirin. (1983). https://pubmed.ncbi.nlm.nih.gov/6411052/ DOI: 10.1161/01.atv.3.4.383

evidence_span

{"source_cache": "artifacts/aspirin-research/7552725.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd61431f20eb312313942bc8a89f970d5d2e33600b32abe692f20d9d5c57d7b1", "start_char": 0, "end_char": 751, "text_sha256": "dd61431f20eb312313942bc8a89f970d5d2e33600b32abe692f20d9d5c57d7b1"}

experimental_model

X-ray crystal structure at 3.4 angstrom of prostaglandin H2 synthase-1 inactivated by a potent aspirin analogue

exposure

2-bromoacetoxy-benzoic acid acetylation, with salicylic acid soaked into the structure

limitations

Direct structural evidence rather than inference from mutants, though at modest resolution and using an analogue rather than aspirin itself.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Enzyme

plain_language

The breakdown product sits in the same place the drug needs to reach, and gets in its way.

primary_references

[asa-p7552725] The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. (1995). https://pubmed.ncbi.nlm.nih.gov/7552725/ DOI: 10.1038/nsb0895-637

tissue_or_cell_type

Crystallised prostaglandin H2 synthase-1

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 143–154

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystal structure at 3.4 angstrom of prostaglandin H2 synthase-1 inactivated by a potent aspirin analogue · source_derived_draft · unverified_draft

### asa-salicylate-antagonises-at-the-site In the crystal structure of the inactivated enzyme the product salicylic acid was observed binding at a site consistent with its antagonistic effect on aspirin activity. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The breakdown product sits in the same place the drug needs to reach, and gets in its way. organism: Enzyme tissue_or_cell_type: Crystallised prostaglandin H2 synthase-1 experimental_model: X-ray crystal structure at 3.4 angstrom of prostaglandin H2 synthase-1 inactivated by a potent aspirin analogue limitations: Direct structural evidence rather than inference from mutants, though at modest resolution and using an analogue rather than aspirin itself. exposure: 2-bromoacetoxy-benzoic acid acetylation, with salicylic acid soaked into the structure evidence_span: {"source_cache": "artifacts/aspirin-research/7552725.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd61431f20eb312313942bc8a89f970d5d2e33600b32abe692f20d9d5c57d7b1", "start_char": 0, "end_char": 751, "text_sha256": "dd61431f20eb312313942bc8a89f970d5d2e33600b32abe692f20d9d5c57d7b1"} [asa-p7552725] The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. (1995). https://pubmed.ncbi.nlm.nih.gov/7552725/ DOI: 10.1038/nsb0895-637

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/aspirin-research/25385584.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b2de8f18887f336c8c735f7ffbd1b72b92e5da43aa6388c229590dea120439f2", "start_char": 0, "end_char": 1242, "text_sha256": "b2de8f18887f336c8c735f7ffbd1b72b92e5da43aa6388c229590dea120439f2"}

experimental_model

Mass-spectrometric assay of cyclooxygenase-1 acetylation in platelets from volunteers given an NSAID followed by aspirin

exposure

A single therapeutic dose of ibuprofen, naproxen or celecoxib followed by 325 milligrams of aspirin

limitations

Measures target engagement directly rather than inferring it from platelet function, and separates the drugs. A single dose of each, in volunteers rather than patients.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

Ibuprofen and naproxen block aspirin in people; celecoxib does not.

primary_references

[asa-p25385584] Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs. (2014). https://pubmed.ncbi.nlm.nih.gov/25385584/ DOI: 10.1073/pnas.1406997111

tissue_or_cell_type

Platelets

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 455–466

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mass-spectrometric assay of cyclooxygenase-1 acetylation in platelets from volunteers given an NSAID followed by aspirin · source_derived_draft · unverified_draft

### asa-which-nsaids-interact Although ibuprofen, naproxen and celecoxib all had the potential to compete with aspirin for access to the substrate binding channel of cyclooxygenase-1 in vitro, measuring aspirin target engagement directly by mass spectrometry after a single therapeutic dose of each followed by 325 milligrams of aspirin revealed a potent drug-drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. Condition category: biomarker_context nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Ibuprofen and naproxen block aspirin in people; celecoxib does not. organism: Human tissue_or_cell_type: Platelets experimental_model: Mass-spectrometric assay of cyclooxygenase-1 acetylation in platelets from volunteers given an NSAID followed by aspirin limitations: Measures target engagement directly rather than inferring it from platelet function, and separates the drugs. A single dose of each, in volunteers rather than patients. exposure: A single therapeutic dose of ibuprofen, naproxen or celecoxib followed by 325 milligrams of aspirin evidence_span: {"source_cache": "artifacts/aspirin-research/25385584.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b2de8f18887f336c8c735f7ffbd1b72b92e5da43aa6388c229590dea120439f2", "start_char": 0, "end_char": 1242, "text_sha256": "b2de8f18887f336c8c735f7ffbd1b72b92e5da43aa6388c229590dea120439f2"} [asa-p25385584] Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs. (2014). https://pubmed.ncbi.nlm.nih.gov/25385584/ DOI: 10.1073/pnas.1406997111

evidence_span

{"source_cache": "artifacts/ibuprofen-research/3303291.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7", "start_char": 0, "end_char": 1757, "text_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7"}

experimental_model

Review of gastroduodenal defence with isolated mucosal preparations

exposure

Acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin on bicarbonate transport and glycoprotein synthesis

limitations

A review of mechanisms rather than an outcome study. The claim that E-series prostaglandins reverse the effect is what ties it to cyclooxygenase.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Human and animal

plain_language

The stomach’s own defences are built by prostaglandins, so blocking them removes the coat rather than adding an acid.

primary_references

[ibu-p3303291] Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents. (1987). https://pubmed.ncbi.nlm.nih.gov/3303291/ DOI: 10.3109/00365528709090947

tissue_or_cell_type

Gastric and duodenal mucosa

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 500–511

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of gastroduodenal defence with isolated mucosal preparations · source_derived_draft · unverified_draft

### ibu-bicarbonate-and-mucus A range of non-steroidal anti-inflammatory agents including acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin inhibit gastric bicarbonate transport in isolated mucosal preparations, effects which can be antagonised by exogenous prostaglandins of the E series, and while the secreted mucus gel overlying the epithelial surface is not affected in the short term a number of these agents inhibit glycoprotein biosynthesis by the epithelial cells, so that loss of this protective coat could be anticipated during chronic exposure as erosion by luminal shear and proteolysis would not be compensated by continued secretion. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The stomach’s own defences are built by prostaglandins, so blocking them removes the coat rather than adding an acid. organism: Human and animal tissue_or_cell_type: Gastric and duodenal mucosa experimental_model: Review of gastroduodenal defence with isolated mucosal preparations limitations: A review of mechanisms rather than an outcome study. The claim that E-series prostaglandins reverse the effect is what ties it to cyclooxygenase. exposure: Acetylsalicylic acid, fenclofenac, ibuprofen and indomethacin on bicarbonate transport and glycoprotein synthesis evidence_span: {"source_cache": "artifacts/ibuprofen-research/3303291.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7", "start_char": 0, "end_char": 1757, "text_sha256": "8609926e51d2ad349198eb5f3ad78b6b552e8f4d4fc74d07bb3a58795a86e7a7"} [ibu-p3303291] Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents. (1987). https://pubmed.ncbi.nlm.nih.gov/3303291/ DOI: 10.3109/00365528709090947

evidence_span

{"source_cache": "artifacts/ibuprofen-research/9060042.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543", "start_char": 0, "end_char": 1394, "text_sha256": "2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543"}

experimental_model

Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay

exposure

Ibuprofen compared against acetylsalicylic acid, sulindac, acetaminophen, ketoprofen and naproxen

limitations

The comparator set is what distinguishes this from a class effect: five other drugs failed. The concentration required is high, and the authors relate it to peak plasma levels rather than measuring them.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Rat

plain_language

Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal.

primary_references

[ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x

tissue_or_cell_type

Cerebellar membranes

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 448–459

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay · source_derived_draft · unverified_draft

### ibu-blocks-anandamide-breakdown The time-dependent reduction in potency of anandamide toward inhibition of cannabinoid agonist binding in rat cerebellar membranes was blocked by ibuprofen but not by acetylsalicylic acid, sulindac, acetaminophen or to any significant extent by ketoprofen and naproxen, a direct assay of anandamide amidase gave a half-maximal inhibitory concentration for ibuprofen of approximately 400 micromolar, and that potency was of the same order as required for inhibition of cyclooxygenase-2 in cell-free systems and as the peak plasma concentrations following a two times 200 milligram dose regimen, so following therapeutic doses the metabolism of anandamide may be affected. Condition category: normal nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: Ibuprofen, and not the other painkillers tested, slows the destruction of the body’s own cannabis-like signal. organism: Rat tissue_or_cell_type: Cerebellar membranes experimental_model: Rat cerebellar membrane preparations assayed by time-dependent loss of anandamide potency and by direct amidase assay limitations: The comparator set is what distinguishes this from a class effect: five other drugs failed. The concentration required is high, and the authors relate it to peak plasma levels rather than measuring them. exposure: Ibuprofen compared against acetylsalicylic acid, sulindac, acetaminophen, ketoprofen and naproxen evidence_span: {"source_cache": "artifacts/ibuprofen-research/9060042.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543", "start_char": 0, "end_char": 1394, "text_sha256": "2c89a26f3812060e97e7bb481126a90840282d64348fc8d4ae9d1dcc7f0a4543"} [ibu-p9060042] Ibuprofen inhibits the metabolism of the endogenous cannabimimetic agent anandamide. (1997). https://pubmed.ncbi.nlm.nih.gov/9060042/ DOI: 10.1111/j.1600-0773.1997.tb00291.x

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ibuprofen-research/696734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139", "start_char": 0, "end_char": 949, "text_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139"}

experimental_model

Clinical case report of an adverse reaction in an aspirin-sensitive asthmatic

exposure

A single 400 milligram ibuprofen tablet in a 53-year-old aspirin-sensitive asthmatic with nasal polyps

limitations

A single case, but it identifies the basis of the reaction as shared pharmacology rather than immunology, which is what determines whether a substitute drug is safe.

nutrient_topic

Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. · Ibuprofen

organism

Human

plain_language

The reaction is not an allergy to the drug but to what the drug does, so any drug that does the same thing will do it too.

primary_references

[ibu-p696734] Cross-reactivity between aspirin and ibuprofen in an asthmatic--a case report. (1978). https://pubmed.ncbi.nlm.nih.gov/696734/ DOI: 10.1093/ajhp/35.10.1245

tissue_or_cell_type

Airway and skin

trigger_kind

biomarker_context Imported condition classification; unverified.

Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (2026-09-22) · lines 539–550

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical case report of an adverse reaction in an aspirin-sensitive asthmatic · source_derived_draft · unverified_draft

### ibu-cross-reacts-pharmacologically A 53-year-old aspirin-sensitive asthmatic man with nasal polyps developed an urticarial rash, laboured breathing, laryngeal oedema and chest tightness after a 400 milligram ibuprofen tablet, requiring isoproterenol, subcutaneous epinephrine, intramuscular diphenhydramine and intravenous hydrocortisone; the reaction was not mediated immunologically but resulted from the prostaglandin synthetase inhibitor activity shared by aspirin, ibuprofen and other analgesics, so selection of an analgesic for an aspirin-sensitive patient should be based on that activity. Condition category: biomarker_context nutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers. plain_language: The reaction is not an allergy to the drug but to what the drug does, so any drug that does the same thing will do it too. organism: Human tissue_or_cell_type: Airway and skin experimental_model: Clinical case report of an adverse reaction in an aspirin-sensitive asthmatic limitations: A single case, but it identifies the basis of the reaction as shared pharmacology rather than immunology, which is what determines whether a substitute drug is safe. exposure: A single 400 milligram ibuprofen tablet in a 53-year-old aspirin-sensitive asthmatic with nasal polyps evidence_span: {"source_cache": "artifacts/ibuprofen-research/696734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139", "start_char": 0, "end_char": 949, "text_sha256": "ca9f025b68310a2b49def4e15ad6f25fb14fc900284de8d68cd80aa6a7f47139"} [ibu-p696734] Cross-reactivity between aspirin and ibuprofen in an asthmatic--a case report. (1978). https://pubmed.ncbi.nlm.nih.gov/696734/ DOI: 10.1093/ajhp/35.10.1245

dose

Increasing tartrazine doses up to 25 mg; positive open challenges repeated double blind

duration

Acute challenge; exact observation window not specified in abstract

evidence_access

Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_scope

literature_reviewed; source-specific experimental curation

experimental_model

156 patients with confirmed aspirin-induced asthma in a multicenter study

limitations

Four confirmed reactions do not establish universal aspirin-tartrazine cross-reactivity or a shared IgE/COX mechanism. Results are specific to the recruited population.

nutrient_topic

Tartrazine food-colorant chapter; nutrient, drug and peptide interactions retain their models and limits. · Tartrazine

organism

156 patients with confirmed aspirin-induced asthma in a multicenter study

plain_language

Four of 156 aspirin-intolerant asthmatics had a double-blind-confirmed tartrazine response with more than a 25% FEV1 fall and symptoms.

primary_references

Intolerance to tartrazine in aspirin-induced asthma: results of a multicenter study. (1988). https://pubmed.ncbi.nlm.nih.gov/3387687/ DOI: 10.1159/000195391

route

Oral tartrazine; aspirin intolerance was a selection criterion, not co-administration

tissue

Oral challenge, spirometry and symptoms

Tartrazine: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 325–334

Original AI-assisted curation of eighteen primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · 156 patients with confirmed aspirin-induced asthma in a multicenter study · source_derived_draft · unverified_draft

## tartrazine-aspirin-asthma Four of 156 aspirin-intolerant asthmatics had a double-blind-confirmed tartrazine response with more than a 25% FEV1 fall and symptoms. Model/species: 156 patients with confirmed aspirin-induced asthma in a multicenter study Tissue: Oral challenge, spirometry and symptoms Exposure: Increasing tartrazine doses up to 25 mg; positive open challenges repeated double blind Route: Oral tartrazine; aspirin intolerance was a selection criterion, not co-administration Duration: Acute challenge; exact observation window not specified in abstract Limits: Four confirmed reactions do not establish universal aspirin-tartrazine cross-reactivity or a shared IgE/COX mechanism. Results are specific to the recruited population. Primary reference: Intolerance to tartrazine in aspirin-induced asthma: results of a multicenter study. (1988). https://pubmed.ncbi.nlm.nih.gov/3387687/ DOI: 10.1159/000195391 Access: Primary PubMed abstract; unrecovered method details explicitly retained.

evidence_span

{"source_cache": "artifacts/paracetamol-research/4588122.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "274f00794352ea4d44e1ef2c2cf46a094d9a03752d7c485a2d6222e519534aa9", "start_char": 0, "end_char": 2254, "text_sha256": "274f00794352ea4d44e1ef2c2cf46a094d9a03752d7c485a2d6222e519534aa9"}

experimental_model

Cisternal cerebrospinal fluid sampled from unanaesthetised cats during fever and after antipyretics

exposure

Shigella dysenteriae pyrogen given into the third ventricle, cisterna magna or intravenously, with indomethacin, paracetamol and aspirin

limitations

Bioassay on a stomach strip rather than direct measurement, and prostaglandin E-like activity rather than identified prostaglandin E2. It is the record that connects fever to central prostaglandin and to this drug.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Cat

plain_language

Fever raises a prostaglandin in the fluid round the brain, and this drug brings both down together.

primary_references

[apap-p4588122] Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats. (1973). https://pubmed.ncbi.nlm.nih.gov/4588122/ DOI: 10.1113/jphysiol.1973.sp010346

tissue_or_cell_type

Cerebrospinal fluid and hypothalamus

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 285–296

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cisternal cerebrospinal fluid sampled from unanaesthetised cats during fever and after antipyretics · source_derived_draft · unverified_draft

### apap-antipyresis-follows-central-prostaglandin Prostaglandin E-like activity in cisternal cerebrospinal fluid was usually undetectable or low at normal body temperature and increased, often many-fold, during pyrogen fever irrespective of the route of pyrogen administration, and the antipyretic drugs indomethacin, paracetamol and aspirin injected intraperitoneally during the fever brought down temperature and returned the activity to low levels, with chromatography placing the activity in the zone of the E series prostaglandins, supporting the theory that pyrogens produce fever by increasing prostaglandin synthesis in the preoptic anterior hypothalamic area and that antipyretics of the aspirin type act by inhibiting that synthesis. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Fever raises a prostaglandin in the fluid round the brain, and this drug brings both down together. organism: Cat tissue_or_cell_type: Cerebrospinal fluid and hypothalamus experimental_model: Cisternal cerebrospinal fluid sampled from unanaesthetised cats during fever and after antipyretics limitations: Bioassay on a stomach strip rather than direct measurement, and prostaglandin E-like activity rather than identified prostaglandin E2. It is the record that connects fever to central prostaglandin and to this drug. exposure: Shigella dysenteriae pyrogen given into the third ventricle, cisterna magna or intravenously, with indomethacin, paracetamol and aspirin evidence_span: {"source_cache": "artifacts/paracetamol-research/4588122.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "274f00794352ea4d44e1ef2c2cf46a094d9a03752d7c485a2d6222e519534aa9", "start_char": 0, "end_char": 2254, "text_sha256": "274f00794352ea4d44e1ef2c2cf46a094d9a03752d7c485a2d6222e519534aa9"} [apap-p4588122] Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats. (1973). https://pubmed.ncbi.nlm.nih.gov/4588122/ DOI: 10.1113/jphysiol.1973.sp010346

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/paracetamol-research/2666482.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b", "start_char": 0, "end_char": 1081, "text_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b"}

experimental_model

Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects

exposure

1000 to 2000 milligram acetaminophen challenges, with aspirin desensitisation and acetaminophen desensitisation

limitations

Three subjects, selected for a history of reacting, so the frequency of cross-reactivity cannot be read from it. The cross-desensitisation result is what identifies the shared mechanism.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Human

plain_language

Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work.

primary_references

[apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. (1989). https://pubmed.ncbi.nlm.nih.gov/2666482/ DOI: 10.1016/0091-6749(89)90174-7

tissue_or_cell_type

Airway

trigger_kind

biomarker_context Imported condition classification; unverified.

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 454–465

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects · source_derived_draft · unverified_draft

### apap-cross-desensitisation-shows-shared-mechanism Three aspirin-sensitive asthmatic subjects with a history of reactions underwent double-blind placebo-controlled challenges and reacted to 1000 milligrams of acetaminophen with a greater than 20% fall in forced expiratory volume in one second, two were desensitized to aspirin and then rechallenged with 1000 milligrams of acetaminophen without reaction, and two were desensitized to acetaminophen achieving refractoriness to 1500 but not 2000 milligrams, so cross sensitivity was documented at large challenge doses and the cross desensitization suggests similar mechanisms are responsible for reactions to aspirin, non-steroidal anti-inflammatory drugs and acetaminophen. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work. organism: Human tissue_or_cell_type: Airway experimental_model: Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects limitations: Three subjects, selected for a history of reacting, so the frequency of cross-reactivity cannot be read from it. The cross-desensitisation result is what identifies the shared mechanism. exposure: 1000 to 2000 milligram acetaminophen challenges, with aspirin desensitisation and acetaminophen desensitisation evidence_span: {"source_cache": "artifacts/paracetamol-research/2666482.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b", "start_char": 0, "end_char": 1081, "text_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b"} [apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. (1989). https://pubmed.ncbi.nlm.nih.gov/2666482/ DOI: 10.1016/0091-6749(89)90174-7

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/paracetamol-research/10400483.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605", "start_char": 0, "end_char": 2662, "text_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605"}

experimental_model

Elective oral challenges in 256 patients with a history of pseudoallergic skin reactions to non-steroidal anti-inflammatory drugs

exposure

Increasing doses of acetaminophen and nimesulide across three patient groups

limitations

A large challenge series that puts a rate on the cross-reactivity and identifies risk factors. Patients were selected for a history of reacting, so the rates apply to that population and not to the general one.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Human

plain_language

One patient in five who reacts to aspirin also reacts to paracetamol, so it is not automatically the safe substitute.

primary_references

[apap-p10400483] Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders. (1999). https://pubmed.ncbi.nlm.nih.gov/10400483/ DOI: 10.1016/s1081-1206(10)63166-3

tissue_or_cell_type

Skin

trigger_kind

biomarker_context Imported condition classification; unverified.

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 467–478

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Elective oral challenges in 256 patients with a history of pseudoallergic skin reactions to non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

### apap-twenty-percent-cross-react Of 256 patients with a history of recent pseudoallergic skin reactions caused by non-steroidal anti-inflammatory drugs who underwent elective oral challenges, 48 or 19% reacted to acetaminophen or nimesulide, with similar proportions among those with chronic urticaria at 23% and otherwise normal subjects with a history of aspirin-induced urticaria at 19% while pyrazolone-intolerant patients showed the lowest number at 4%, aspirin intolerance was a risk factor for acetaminophen or nimesulide induced urticaria with a relative risk of 5.4, a history of anaphylactoid reactions carried a relative risk of 5.7, and atopy raised reactivity to nimesulide from 9 to 23%. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: One patient in five who reacts to aspirin also reacts to paracetamol, so it is not automatically the safe substitute. organism: Human tissue_or_cell_type: Skin experimental_model: Elective oral challenges in 256 patients with a history of pseudoallergic skin reactions to non-steroidal anti-inflammatory drugs limitations: A large challenge series that puts a rate on the cross-reactivity and identifies risk factors. Patients were selected for a history of reacting, so the rates apply to that population and not to the general one. exposure: Increasing doses of acetaminophen and nimesulide across three patient groups evidence_span: {"source_cache": "artifacts/paracetamol-research/10400483.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605", "start_char": 0, "end_char": 2662, "text_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605"} [apap-p10400483] Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders. (1999). https://pubmed.ncbi.nlm.nih.gov/10400483/ DOI: 10.1016/s1081-1206(10)63166-3

evidence_span

{"source_cache": "artifacts/aspirin-research/6792646.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55b09486e54c42e6ecdac3476a0ae8b9d9819f06b5b01a9fc33087fd621a9c82", "start_char": 0, "end_char": 767, "text_sha256": "55b09486e54c42e6ecdac3476a0ae8b9d9819f06b5b01a9fc33087fd621a9c82"}

experimental_model

Electrically induced carotid artery thrombosis in male rats with salicylate pretreatment

exposure

Sodium salicylate 15 or 100 milligrams per kilogram intravenously two minutes before aspirin 10 milligrams per kilogram

limitations

A direct in vivo test of an in vitro observation. One model, one species, and thrombus generation measured indirectly by downstream temperature.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Rat

plain_language

The metabolite gets in the drug’s way in a test tube, but giving it first did not stop aspirin working in a rat.

primary_references

[asa-p6792646] Non-interference by salicylate with aspirin inhibition of arterial thrombosis in rats. (1981). https://pubmed.ncbi.nlm.nih.gov/6792646/ DOI: 10.1016/0161-4630(81)90052-5

tissue_or_cell_type

Carotid artery

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 520–531

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrically induced carotid artery thrombosis in male rats with salicylate pretreatment · source_derived_draft · unverified_draft

### asa-antagonism-not-seen-in-vivo Several authors have reported that salicylate blocks and reverses aspirin inhibition of prostaglandin synthesis by platelets and arterial wall, but when rats were given sodium salicylate at 15 or 100 milligrams per kilogram two minutes before aspirin at 10 milligrams per kilogram, a significant antithrombotic effect of aspirin was observed in all cases regardless of prior salicylate administration with results similar to aspirin alone, so competition between salicylate and aspirin as reported in vitro does not appear to significantly affect the in vivo antithrombotic action in this model. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The metabolite gets in the drug’s way in a test tube, but giving it first did not stop aspirin working in a rat. organism: Rat tissue_or_cell_type: Carotid artery experimental_model: Electrically induced carotid artery thrombosis in male rats with salicylate pretreatment limitations: A direct in vivo test of an in vitro observation. One model, one species, and thrombus generation measured indirectly by downstream temperature. exposure: Sodium salicylate 15 or 100 milligrams per kilogram intravenously two minutes before aspirin 10 milligrams per kilogram evidence_span: {"source_cache": "artifacts/aspirin-research/6792646.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55b09486e54c42e6ecdac3476a0ae8b9d9819f06b5b01a9fc33087fd621a9c82", "start_char": 0, "end_char": 767, "text_sha256": "55b09486e54c42e6ecdac3476a0ae8b9d9819f06b5b01a9fc33087fd621a9c82"} [asa-p6792646] Non-interference by salicylate with aspirin inhibition of arterial thrombosis in rats. (1981). https://pubmed.ncbi.nlm.nih.gov/6792646/ DOI: 10.1016/0161-4630(81)90052-5

evidence_span

{"source_cache": "artifacts/aspirin-research/8052854.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d1d488e1bc53706da4f733f3fecc2bb981c09c0aa2dccae2bac9fac1bb04cec1", "start_char": 0, "end_char": 737, "text_sha256": "d1d488e1bc53706da4f733f3fecc2bb981c09c0aa2dccae2bac9fac1bb04cec1"}

experimental_model

Electrophoretic mobility shift and reporter transcription assays in transfected T cells

exposure

Sodium salicylate and aspirin applied to nuclear factor kappa B activation

limitations

A cell-based mechanism recorded at the concentrations used in the assay, which are far above those reached by antiplatelet dosing. It does not distinguish the two compounds from one another.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Human cells

plain_language

Both compounds keep an inflammatory master switch locked out of the nucleus.

primary_references

[asa-p8052854] Inhibition of NF-kappa B by sodium salicylate and aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8052854/ DOI: 10.1126/science.8052854

tissue_or_cell_type

T lymphocytes

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 468–479

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophoretic mobility shift and reporter transcription assays in transfected T cells · source_derived_draft · unverified_draft

### asa-salicylate-blocks-nfkb The anti-inflammatory drugs sodium salicylate and aspirin inhibited activation of nuclear factor kappa B, an inhibition which prevented degradation of the inhibitor I-kappa-B so that nuclear factor kappa B was retained in the cytosol, and both also inhibited nuclear factor kappa B-dependent transcription from the immunoglobulin kappa enhancer and the human immunodeficiency virus long terminal repeat in transfected T cells. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Both compounds keep an inflammatory master switch locked out of the nucleus. organism: Human cells tissue_or_cell_type: T lymphocytes experimental_model: Electrophoretic mobility shift and reporter transcription assays in transfected T cells limitations: A cell-based mechanism recorded at the concentrations used in the assay, which are far above those reached by antiplatelet dosing. It does not distinguish the two compounds from one another. exposure: Sodium salicylate and aspirin applied to nuclear factor kappa B activation evidence_span: {"source_cache": "artifacts/aspirin-research/8052854.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d1d488e1bc53706da4f733f3fecc2bb981c09c0aa2dccae2bac9fac1bb04cec1", "start_char": 0, "end_char": 737, "text_sha256": "d1d488e1bc53706da4f733f3fecc2bb981c09c0aa2dccae2bac9fac1bb04cec1"} [asa-p8052854] Inhibition of NF-kappa B by sodium salicylate and aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8052854/ DOI: 10.1126/science.8052854

evidence_span

{"source_cache": "artifacts/aspirin-research/7064099.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1e175ec209c9a177b7514b5931c3b02d3ca7c09a0d3629d55fcbd2b2f9088b4", "start_char": 0, "end_char": 1514, "text_sha256": "b1e175ec209c9a177b7514b5931c3b02d3ca7c09a0d3629d55fcbd2b2f9088b4"}

experimental_model

Measurement of intramural pH in the antral mucosa with ulceration scoring across luminal pH and routes of administration

exposure

Luminal and intravenous sodium salicylate and acetylsalicylic acid at luminal pH 7, 3.5 and 1

limitations

Separates the two compounds and the two routes against a controlled luminal acidity. The comparison of prostaglandin effects is stated rather than measured in this study.

nutrient_topic

Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

organism

Animal

plain_language

The metabolite, which does not touch prostaglandins, ulcerates the stomach just as the drug does, so prostaglandins are not the whole story.

primary_references

[asa-p7064099] Effects of sodium salicylate and acetylsalicylic acid on intramural pH and ulceration of rabbit antral mucosa. (1982). https://pubmed.ncbi.nlm.nih.gov/7064099/

tissue_or_cell_type

Gastric antral mucosa

Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 533–544

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Measurement of intramural pH in the antral mucosa with ulceration scoring across luminal pH and routes of administration · source_derived_draft · unverified_draft

### asa-ulceration-without-prostaglandins Neither sodium salicylate nor acetylsalicylic acid given intravenously affected intramural pH or caused ulceration at luminal pH 7 or 3.5, but at luminal pH 1 both compounds caused ulceration and subtle changes in net ion fluxes without altering intramural pH, and since intravenous sodium salicylate and acetylsalicylic acid both cause ulceration but only acetylsalicylic acid alters prostaglandin synthesis, interference with prostaglandin metabolism does not appear to be a prerequisite for the occurrence of ulceration. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The metabolite, which does not touch prostaglandins, ulcerates the stomach just as the drug does, so prostaglandins are not the whole story. organism: Animal tissue_or_cell_type: Gastric antral mucosa experimental_model: Measurement of intramural pH in the antral mucosa with ulceration scoring across luminal pH and routes of administration limitations: Separates the two compounds and the two routes against a controlled luminal acidity. The comparison of prostaglandin effects is stated rather than measured in this study. exposure: Luminal and intravenous sodium salicylate and acetylsalicylic acid at luminal pH 7, 3.5 and 1 evidence_span: {"source_cache": "artifacts/aspirin-research/7064099.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1e175ec209c9a177b7514b5931c3b02d3ca7c09a0d3629d55fcbd2b2f9088b4", "start_char": 0, "end_char": 1514, "text_sha256": "b1e175ec209c9a177b7514b5931c3b02d3ca7c09a0d3629d55fcbd2b2f9088b4"} [asa-p7064099] Effects of sodium salicylate and acetylsalicylic acid on intramural pH and ulceration of rabbit antral mucosa. (1982). https://pubmed.ncbi.nlm.nih.gov/7064099/