Indomethacin

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Rat pharmacological perturbations.

limitations

No human food–drug interaction magnitude was tested.

nutrient_topic

Monosodium Glutamate (MSG) collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Monosodium L-glutamate

plain_language

Mediator synthesis and afferent function constrain the response.

primary_references

Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19643955/ · DOI 10.1152/ajpgi.90605.2008

trigger_kind

machinery_impairment Imported condition classification; unverified.

Monosodium Glutamate (MSG): taste, gut sensing, exposure and cross-nutrient mechanisms (2026-09-20) · lines 210–216

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pharmacological perturbations. · source_derived_draft · unverified_draft

## monosodium-glutamate-duodenal-cox-gate Mediator synthesis and afferent function constrain the response. Indomethacin or capsaicin pretreatment reduced glutamate-associated mucus and pH responses. Model: Rat pharmacological perturbations. Limitations: No human food–drug interaction magnitude was tested. Evidence access: Primary abstract Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19643955/ · DOI 10.1152/ajpgi.90605.2008

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction.

limitations

Small historical study; magnitude is not universal for all NSAIDs.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A medicine can raise lithium exposure by slowing its removal.

primary_references

Indomethacin increases plasma lithium. · 1979 · https://pubmed.ncbi.nlm.nih.gov/444956/ · DOI 10.1136/bmj.1.6171.1115

trigger_kind

biomarker_context Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 376–382

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction. · source_derived_draft · unverified_draft

## lithium-nsaid-clearance A medicine can raise lithium exposure by slowing its removal. Indomethacin raised plasma lithium while lowering renal lithium clearance in seven studied people. Model: Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction. Limitations: Small historical study; magnitude is not universal for all NSAIDs. Evidence access: Primary abstract Indomethacin increases plasma lithium. · 1979 · https://pubmed.ncbi.nlm.nih.gov/444956/ · DOI 10.1136/bmj.1.6171.1115

evidence_access

Primary abstract

experimental_model

200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively.

limitations

Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Sodium intake changes the setting for a drug interaction.

primary_references

Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 368–374

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. · source_derived_draft · unverified_draft

## lithium-sodium-renal-context Sodium intake changes the setting for a drug interaction. Indomethacin increased fractional lithium reabsorption on both high- and low-sodium diets in seven volunteers. Model: 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. Limitations: Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker. Evidence access: Primary abstract Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/

evidence_span

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experimental_model

Kinetics of recovery of platelet thromboxane production after single doses, with platelets resuspended in drug-free plasma

exposure

Indomethacin and ibuprofen compared, with isolated platelets and platelet microsomes

limitations

The resuspension experiment is what separates a reversible inhibitor from a slowly reversible one. It uses indomethacin as the contrast and reports ibuprofen as the reference reversible drug.

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

Wash the drug away and the platelet enzyme is working again at once, which is the opposite of what aspirin does.

primary_references

[ibu-p3088675] Time-dependent inhibition of platelet cyclooxygenase by indomethacin is slowly reversible. (1986). https://pubmed.ncbi.nlm.nih.gov/3088675/ DOI: 10.1016/0090-6980(86)90170-x

tissue_or_cell_type

Platelets

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 279–290

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics of recovery of platelet thromboxane production after single doses, with platelets resuspended in drug-free plasma · source_derived_draft · unverified_draft

### ibu-ibuprofen-washes-straight-out When platelets were isolated and resuspended in homologous drug-free plasma, slow recovery of thromboxane production was seen after indomethacin with 50% of control activity regained in 100 minutes, whereas ibuprofen-treated platelets, exposed to a competitive inhibitor of cyclooxygenase, recovered nearly completely immediately on being resuspended in drug-free plasma. 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: Wash the drug away and the platelet enzyme is working again at once, which is the opposite of what aspirin does. organism: Human tissue_or_cell_type: Platelets experimental_model: Kinetics of recovery of platelet thromboxane production after single doses, with platelets resuspended in drug-free plasma limitations: The resuspension experiment is what separates a reversible inhibitor from a slowly reversible one. It uses indomethacin as the contrast and reports ibuprofen as the reference reversible drug. exposure: Indomethacin and ibuprofen compared, with isolated platelets and platelet microsomes evidence_span: {"source_cache": "artifacts/ibuprofen-research/3088675.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee49ae775f6c268fd63afc816cda206f0bdab5efe9ce86b4f97fd8ee6bda3a1a", "start_char": 0, "end_char": 1400, "text_sha256": "ee49ae775f6c268fd63afc816cda206f0bdab5efe9ce86b4f97fd8ee6bda3a1a"} [ibu-p3088675] Time-dependent inhibition of platelet cyclooxygenase by indomethacin is slowly reversible. (1986). https://pubmed.ncbi.nlm.nih.gov/3088675/ DOI: 10.1016/0090-6980(86)90170-x

evidence_span

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experimental_model

Regional vascular resistance measurement in pentobarbital-anaesthetised dogs

exposure

Indomethacin and ibuprofen given intravenously and intra-arterially, including a 50 milligram intravenous bolus

limitations

A direct head-to-head between two drugs of the same class in the same animals, with a negative result for ibuprofen. Anaesthetised dogs.

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

Dog

plain_language

One drug of this class strangles the gut circulation and the other does not, and it is not a prostaglandin effect.

primary_references

[ibu-p7299691] Differential effects of ibuprofen and indomethacin in the regional circulation of the dog. (1981). https://pubmed.ncbi.nlm.nih.gov/7299691/ DOI: 10.1016/s0022-3565(25)32861-2

tissue_or_cell_type

Mesenteric and renal circulations

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 487–498

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Regional vascular resistance measurement in pentobarbital-anaesthetised dogs · source_derived_draft · unverified_draft

### ibu-not-a-class-effect Indomethacin produced severe acute mesenteric vasoconstriction by intravenous infusion and by intra-arterial injection with rapid tachyphylaxis, whereas ibuprofen did not alter mesenteric blood flow even when a large 50 milligram bolus was rapidly injected, and the indomethacin response was not modified when prostaglandin synthesis was inhibited nor significantly mediated by alpha adrenergic agents or serotonin, while both drugs raised aortic pressure and reduced renal blood flow by small but significant amounts. 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: One drug of this class strangles the gut circulation and the other does not, and it is not a prostaglandin effect. organism: Dog tissue_or_cell_type: Mesenteric and renal circulations experimental_model: Regional vascular resistance measurement in pentobarbital-anaesthetised dogs limitations: A direct head-to-head between two drugs of the same class in the same animals, with a negative result for ibuprofen. Anaesthetised dogs. exposure: Indomethacin and ibuprofen given intravenously and intra-arterially, including a 50 milligram intravenous bolus evidence_span: {"source_cache": "artifacts/ibuprofen-research/7299691.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "217a7f084ce5301b9b357bed0af13552ba7114c56c9d2692852bd4581450a02d", "start_char": 0, "end_char": 1542, "text_sha256": "217a7f084ce5301b9b357bed0af13552ba7114c56c9d2692852bd4581450a02d"} [ibu-p7299691] Differential effects of ibuprofen and indomethacin in the regional circulation of the dog. (1981). https://pubmed.ncbi.nlm.nih.gov/7299691/ DOI: 10.1016/s0022-3565(25)32861-2

evidence_span

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experimental_model

Chinese hamster ovary cell lines stably expressing each human cyclooxygenase isoform, with cell-free comparison

exposure

Ibuprofen, indomethacin, NS-398 and DuP-697 across intact cells and microsomal preparations

limitations

Shows that the selectivity numbers depend on the assay, which bears on every potency ratio quoted for this drug class. A heterologous expression system.

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 enzyme in hamster cells

plain_language

Against both enzymes it is a reversible blocker, and the numbers you get depend on which assay you use.

primary_references

[ibu-p8831731] Mechanism of selective inhibition of human prostaglandin G/H synthase-1 and -2 in intact cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8831731/ DOI: 10.1016/0006-2952(96)00462-5

tissue_or_cell_type

Intact cells and cell-free preparations

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 292–303

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chinese hamster ovary cell lines stably expressing each human cyclooxygenase isoform, with cell-free comparison · source_derived_draft · unverified_draft

### ibu-reversible-against-both-isoforms Reversible inhibition of both cellular cyclooxygenase-1 and cyclooxygenase-2 was observed with the nonselective drugs ibuprofen and indomethacin, whereas the selective inhibitor DuP-697 was reversible against cyclooxygenase-1 but irreversible against cyclooxygenase-2, and indomethacin displayed time-dependent inhibition of both cellular isoforms; the selectivities and potencies of inhibitors determined using intact cells are affected by substrate concentration and differ from those determined in cell-free microsomal or purified enzyme preparations. 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: Against both enzymes it is a reversible blocker, and the numbers you get depend on which assay you use. organism: Human enzyme in hamster cells tissue_or_cell_type: Intact cells and cell-free preparations experimental_model: Chinese hamster ovary cell lines stably expressing each human cyclooxygenase isoform, with cell-free comparison limitations: Shows that the selectivity numbers depend on the assay, which bears on every potency ratio quoted for this drug class. A heterologous expression system. exposure: Ibuprofen, indomethacin, NS-398 and DuP-697 across intact cells and microsomal preparations evidence_span: {"source_cache": "artifacts/ibuprofen-research/8831731.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d3161aac692f44c874cafb498e9606f0382b380662ccb58cd1683139f1c1df99", "start_char": 0, "end_char": 1993, "text_sha256": "d3161aac692f44c874cafb498e9606f0382b380662ccb58cd1683139f1c1df99"} [ibu-p8831731] Mechanism of selective inhibition of human prostaglandin G/H synthase-1 and -2 in intact cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8831731/ DOI: 10.1016/0006-2952(96)00462-5

evidence_span

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experimental_model

Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts

exposure

S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation

limitations

The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined.

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, human and sheep systems

plain_language

At the first enzyme one hand is thirty to ninety times stronger; at the second enzyme the two hands are indistinguishable.

primary_references

[ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x

tissue_or_cell_type

Transfected cells, hepatoma cells, platelets and purified enzyme

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 318–329

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts · source_derived_draft · unverified_draft

### ibu-thirty-two-fold-at-cox1 The S(+) isomer of ibuprofen was 32-, 41- and 96-fold more potent than the R(-) isomer for inhibition of prostaglandin endoperoxide H synthase-1 activity, human platelet aggregation and serotonin secretion respectively, while on prostaglandin endoperoxide H synthase-2 the ibuprofen isomers showed no selectivity, and indomethacin, S(+)-ibuprofen and S(+)-naproxen were 6-, 27- and 5-fold more potent as inhibitors of synthase-1 than of synthase-2. 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: At the first enzyme one hand is thirty to ninety times stronger; at the second enzyme the two hands are indistinguishable. organism: Rat, human and sheep systems tissue_or_cell_type: Transfected cells, hepatoma cells, platelets and purified enzyme experimental_model: Reporter and enzyme assays comparing ibuprofen isomers against naproxen and indomethacin across four readouts limitations: The only record here that measures both enantiomers on the same panel, which is what makes the fold-differences meaningful. Several different assay systems are combined. exposure: S(+)- and R(-)-ibuprofen compared directly on cyclooxygenase-1 and -2, platelet function and nuclear receptor activation evidence_span: {"source_cache": "artifacts/ibuprofen-research/11755111.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239", "start_char": 0, "end_char": 2074, "text_sha256": "1dd77f4a1eebd7777285c424b1731f4744d0fa593e62cfbde0a92dbb6242b239"} [ibu-p11755111] Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin. (2001). https://pubmed.ncbi.nlm.nih.gov/11755111/ DOI: 10.1016/s0006-2952(01)00822-x

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

evidence_span

{"source_cache": "artifacts/paracetamol-research/1727638.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c", "start_char": 0, "end_char": 1789, "text_sha256": "028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c"}

experimental_model

Rapid scan spectrometry and transient state kinetics of prostaglandin H synthase compound II reduction

exposure

Phenol and hydroquinone as reducing cosubstrates, with indomethacin

limitations

Measures the reduction step directly with rate constants rather than inferring it from inhibition. It uses phenol and hydroquinone rather than paracetamol, which is recorded on the claim.

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

Enzyme

plain_language

A phenol hands the enzyme one electron at a time, and enough of it makes the radical the enzyme needs disappear.

primary_references

[apap-p1727638] Reduction of prostaglandin H synthase compound II by phenol and hydroquinone, and the effect of indomethacin. (1992). https://pubmed.ncbi.nlm.nih.gov/1727638/ DOI: 10.1016/0003-9861(92)90070-d

tissue_or_cell_type

Purified prostaglandin H synthase

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 142–153

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rapid scan spectrometry and transient state kinetics of prostaglandin H synthase compound II reduction · source_derived_draft · unverified_draft

### apap-one-electron-reduction Reduction of prostaglandin H synthase compound II to native enzyme by phenol proceeded with a second-order rate constant of 5.3 x 10(5) per molar per second and by hydroquinone at 2.1 x 10(6), rapid scan spectra also showed reduction of compound I to compound II by both so that reduction of both compounds is a one-electron process, and the results suggest the tyrosyl radical detected in the presence of oxidizing agents is formed by intramolecular electron transfer from the tyrosyl residue to the porphyrin pi-cation radical and tends to disappear in the presence of sufficient reducing substrate. 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: A phenol hands the enzyme one electron at a time, and enough of it makes the radical the enzyme needs disappear. organism: Enzyme tissue_or_cell_type: Purified prostaglandin H synthase experimental_model: Rapid scan spectrometry and transient state kinetics of prostaglandin H synthase compound II reduction limitations: Measures the reduction step directly with rate constants rather than inferring it from inhibition. It uses phenol and hydroquinone rather than paracetamol, which is recorded on the claim. exposure: Phenol and hydroquinone as reducing cosubstrates, with indomethacin evidence_span: {"source_cache": "artifacts/paracetamol-research/1727638.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c", "start_char": 0, "end_char": 1789, "text_sha256": "028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c"} [apap-p1727638] Reduction of prostaglandin H synthase compound II by phenol and hydroquinone, and the effect of indomethacin. (1992). https://pubmed.ncbi.nlm.nih.gov/1727638/ DOI: 10.1016/0003-9861(92)90070-d

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

evidence_span

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experimental_model

Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs

exposure

Aspirin acetylation and the methionine mutant, tested with indomethacin, diclofenac, meclofenamic acid and selective inhibitors

limitations

Quantifies how efficient the new activity is, which most descriptions of the switch do not. Purified and recombinant enzyme rather than intact cells.

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

Two common anti-inflammatories cannot touch the rerouted enzyme, because they needed the serine aspirin has taken.

primary_references

[asa-p9016346] Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs. (1997). https://pubmed.ncbi.nlm.nih.gov/9016346/ DOI: 10.1124/mol.51.1.52

tissue_or_cell_type

Cyclooxygenase-2

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 273–284

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

### asa-fenamates-do-not-block-it The production of 15-HETE by aspirin-modified cyclooxygenase-2 was sensitive to inhibition by most non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors and the inhibition by indomethacin was time-dependent, but two potent structurally related drugs, diclofenac and meclofenamic acid, did not inhibit either the acetylated enzyme or the S516M mutant, so Ser516 plays an important role in the interaction with fenamate inhibitors. 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: Two common anti-inflammatories cannot touch the rerouted enzyme, because they needed the serine aspirin has taken. organism: Enzyme tissue_or_cell_type: Cyclooxygenase-2 experimental_model: Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs limitations: Quantifies how efficient the new activity is, which most descriptions of the switch do not. Purified and recombinant enzyme rather than intact cells. exposure: Aspirin acetylation and the methionine mutant, tested with indomethacin, diclofenac, meclofenamic acid and selective inhibitors evidence_span: {"source_cache": "artifacts/aspirin-research/9016346.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b", "start_char": 0, "end_char": 1899, "text_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b"} [asa-p9016346] Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs. (1997). https://pubmed.ncbi.nlm.nih.gov/9016346/ DOI: 10.1124/mol.51.1.52

evidence_span

{"source_cache": "artifacts/aspirin-research/8621937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1", "start_char": 0, "end_char": 1767, "text_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1"}

experimental_model

Adhesion molecule expression, neutrophil adhesion and transendothelial migration in human umbilical vein endothelial cells

exposure

Sodium salicylate against tumour necrosis factor alpha stimulation, with indomethacin as a cyclooxygenase control

limitations

The indomethacin control is the important part: it shows the effect is not a cyclooxygenase effect. High salicylate concentrations, which the authors relate to high-dose therapy rather than to antiplatelet dosing.

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

A cyclooxygenase blocker does nothing here, so this arm of salicylate is not about prostaglandins at all.

primary_references

[asa-p8621937] Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. (1996). https://pubmed.ncbi.nlm.nih.gov/8621937/ DOI: 10.4049/jimmunol.156.10.3961

tissue_or_cell_type

Endothelium

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 481–492

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adhesion molecule expression, neutrophil adhesion and transendothelial migration in human umbilical vein endothelial cells · source_derived_draft · unverified_draft

### asa-not-a-cyclooxygenase-effect Sodium salicylate inhibited activation of nuclear factor kappa B by preventing phosphorylation and subsequent degradation of I-kappa-B-alpha without affecting tumour necrosis factor alpha-induced phosphorylation of ATF-2, blocked the increase in adhesion molecule messenger RNA and gave dose-dependent inhibition of surface vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 with higher doses required for endothelial-leukocyte adhesion molecule 1, and inhibited transendothelial migration of neutrophils; indomethacin, a nonsalicylate cyclooxygenase inhibitor, had no effect on surface expression, suggesting the effects were not due to inhibition of cyclooxygenase. 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: A cyclooxygenase blocker does nothing here, so this arm of salicylate is not about prostaglandins at all. organism: Human cells tissue_or_cell_type: Endothelium experimental_model: Adhesion molecule expression, neutrophil adhesion and transendothelial migration in human umbilical vein endothelial cells limitations: The indomethacin control is the important part: it shows the effect is not a cyclooxygenase effect. High salicylate concentrations, which the authors relate to high-dose therapy rather than to antiplatelet dosing. exposure: Sodium salicylate against tumour necrosis factor alpha stimulation, with indomethacin as a cyclooxygenase control evidence_span: {"source_cache": "artifacts/aspirin-research/8621937.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1", "start_char": 0, "end_char": 1767, "text_sha256": "9b5aff676845bd0a47f25a0f63564880f70af7667b5ab9d667cece58d05356f1"} [asa-p8621937] Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. (1996). https://pubmed.ncbi.nlm.nih.gov/8621937/ DOI: 10.4049/jimmunol.156.10.3961