Salicylate / salicylic acid

evidence_span

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experimental_model

Prostaglandin H synthase inhibition by salicylate compared with phenolic inhibitors, using manganese-reconstituted enzyme

exposure

Salicylate and benzoic acid analogues, with 12-hydroperoxyeicosatetraenoic acid and prostaglandin G2

limitations

Recorded here because it separates paracetamol from salicylate mechanistically while showing both are peroxide-sensitive. The work is on salicylate, which is stated 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

Two drugs that both stop working when peroxide is high, reaching that point by different routes.

primary_references

[apap-p12538810] Inhibition of prostaglandin H2 synthases by salicylate is dependent on the oxidative state of the enzymes. (2003). https://pubmed.ncbi.nlm.nih.gov/12538810/ DOI: 10.1124/jpet.102.042853

tissue_or_cell_type

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 168–179

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prostaglandin H synthase inhibition by salicylate compared with phenolic inhibitors, using manganese-reconstituted enzyme · source_derived_draft · unverified_draft

### apap-salicylate-is-not-a-cosubstrate Salicylate inhibits prostaglandin H synthase-1 and -2 with a potency inversely related to ambient hydroperoxide concentrations and its inhibition of synthase-1 was prevented by 12-hydroperoxyeicosatetraenoic acid, but unlike typical phenolic inhibitors such as acetaminophen, salicylate was ineffective as a reducing cosubstrate for the peroxidase activity, implicating the cyclooxygenase site as its target; 12-HPETE does not prevent inhibition of the manganese-reconstituted enzyme by salicylate, indicating that reversal by hydroperoxides depends on electron transfer between the cyclooxygenase and peroxidase active sites. 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: Two drugs that both stop working when peroxide is high, reaching that point by different routes. organism: Enzyme tissue_or_cell_type: Prostaglandin H synthase experimental_model: Prostaglandin H synthase inhibition by salicylate compared with phenolic inhibitors, using manganese-reconstituted enzyme limitations: Recorded here because it separates paracetamol from salicylate mechanistically while showing both are peroxide-sensitive. The work is on salicylate, which is stated on the claim. exposure: Salicylate and benzoic acid analogues, with 12-hydroperoxyeicosatetraenoic acid and prostaglandin G2 evidence_span: {"source_cache": "artifacts/paracetamol-research/12538810.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "23bbb8a6c280cfcae85e304695c2a93f2c748c804befc1e006f415f4f8dfaed0", "start_char": 0, "end_char": 1592, "text_sha256": "23bbb8a6c280cfcae85e304695c2a93f2c748c804befc1e006f415f4f8dfaed0"} [apap-p12538810] Inhibition of prostaglandin H2 synthases by salicylate is dependent on the oxidative state of the enzymes. (2003). https://pubmed.ncbi.nlm.nih.gov/12538810/ DOI: 10.1124/jpet.102.042853

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

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/aspirin-research/25256746.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2", "start_char": 0, "end_char": 1171, "text_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2"}

experimental_model

Incubation of rat fast-twitch epitrochlearis and slow-twitch soleus muscle with salicylate

exposure

Salicylate applied to isolated muscle with glucose transport and nucleotide measurements

limitations

Adds the tissue and the energy measurements. Isolated muscle at concentrations set by the incubation buffer, which is not a plasma concentration.

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

Muscle takes up more glucose without any help from insulin, and its energy stores fall while it happens.

primary_references

[asa-p25256746] Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles. (2014). https://pubmed.ncbi.nlm.nih.gov/25256746/ DOI: 10.1016/j.bbrc.2014.09.066

tissue_or_cell_type

Skeletal muscle

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 507–518

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Incubation of rat fast-twitch epitrochlearis and slow-twitch soleus muscle with salicylate · source_derived_draft · unverified_draft

### asa-muscle-glucose-uptake Intracellular salicylate concentrations increased within five minutes in both rat fast-twitch and slow-twitch muscle, threonine-172 phosphorylation of the AMP-activated protein kinase alpha subunit increased dose- and time-dependently with increases in both alpha-1 and alpha-2 activity, and these were accompanied by increased 3-O-methyl-D-glucose transport and decreases in ATP, phosphocreatine and glycogen, while phosphorylation of insulin receptor substrate 1, Akt and p70 S6 kinase was unchanged. 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: Muscle takes up more glucose without any help from insulin, and its energy stores fall while it happens. organism: Rat tissue_or_cell_type: Skeletal muscle experimental_model: Incubation of rat fast-twitch epitrochlearis and slow-twitch soleus muscle with salicylate limitations: Adds the tissue and the energy measurements. Isolated muscle at concentrations set by the incubation buffer, which is not a plasma concentration. exposure: Salicylate applied to isolated muscle with glucose transport and nucleotide measurements evidence_span: {"source_cache": "artifacts/aspirin-research/25256746.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2", "start_char": 0, "end_char": 1171, "text_sha256": "e8cd347665e1de7dc2cadee06da087e2526d4fc11aefef6f7ce15cb33f6234c2"} [asa-p25256746] Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles. (2014). https://pubmed.ncbi.nlm.nih.gov/25256746/ DOI: 10.1016/j.bbrc.2014.09.066

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

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/aspirin-research/22517326.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4", "start_char": 0, "end_char": 887, "text_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4"}

experimental_model

Allosteric activation and dephosphorylation assays with AMP-activated protein kinase knockout mice

exposure

Salicylate at concentrations reached in plasma after salsalate or high-dose aspirin, against the synthetic activator A-769662

limitations

The knockout arm ties the whole-animal effect to the kinase. The concentrations are those of high-dose salicylate therapy, not of antiplatelet aspirin, which the authors state explicitly.

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 and mouse

plain_language

The old plant compound switches on the cell’s energy sensor directly, at doses far above a daily aspirin.

primary_references

[asa-p22517326] The ancient drug salicylate directly activates AMP-activated protein kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/22517326/ DOI: 10.1126/science.1215327

tissue_or_cell_type

AMP-activated protein kinase

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 494–505

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Allosteric activation and dephosphorylation assays with AMP-activated protein kinase knockout mice · source_derived_draft · unverified_draft

### asa-salicylate-activates-ampk At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates AMP-activated protein kinase by binding at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site threonine-172, and in knockout mice the effects of salicylate to increase fat utilisation and to lower plasma fatty acids in vivo were lost. 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: The old plant compound switches on the cell’s energy sensor directly, at doses far above a daily aspirin. organism: Human enzyme and mouse tissue_or_cell_type: AMP-activated protein kinase experimental_model: Allosteric activation and dephosphorylation assays with AMP-activated protein kinase knockout mice limitations: The knockout arm ties the whole-animal effect to the kinase. The concentrations are those of high-dose salicylate therapy, not of antiplatelet aspirin, which the authors state explicitly. exposure: Salicylate at concentrations reached in plasma after salsalate or high-dose aspirin, against the synthetic activator A-769662 evidence_span: {"source_cache": "artifacts/aspirin-research/22517326.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4", "start_char": 0, "end_char": 887, "text_sha256": "1a48863bf252421416f67d62acb18c9f44f170075c5aff6f775eba14bba2b1b4"} [asa-p22517326] The ancient drug salicylate directly activates AMP-activated protein kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/22517326/ DOI: 10.1126/science.1215327

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

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/

evidence_span

{"source_cache": "artifacts/paracetamol-research/15035793.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f72415969de66bea6c0588049cbe1fd1a4b23195c0e2f5a60293eaf99a0f641e", "start_char": 0, "end_char": 1279, "text_sha256": "f72415969de66bea6c0588049cbe1fd1a4b23195c0e2f5a60293eaf99a0f641e"}

experimental_model

Review of the mechanism of paracetamol and salicylate as peroxide-sensitive inhibitors

exposure

Paracetamol and salicylate at low arachidonic acid concentrations

limitations

A review proposing a drug class rather than a new measurement. Its argument that apparent cyclooxygenase-2 selectivity arises from flux rather than binding is the useful part.

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 and enzyme

plain_language

The apparent preference for the second enzyme may be nothing to do with binding it, and everything to do with how much peroxide each pathway makes.

primary_references

[apap-p15035793] Mechanisms of action of paracetamol and related analgesics. (2003). https://pubmed.ncbi.nlm.nih.gov/15035793/ DOI: 10.1163/156856003322699573

tissue_or_cell_type

Cyclooxygenase

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 181–192

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the mechanism of paracetamol and salicylate as peroxide-sensitive inhibitors · source_derived_draft · unverified_draft

### apap-apparent-selectivity-from-flux Paracetamol and salicylate are weak inhibitors of both isolated cyclooxygenase-1 and -2 but potent inhibitors of prostaglandin synthesis in intact cells if low concentrations of arachidonic acid are available, the effects of both being overcome by increased hydroperoxide levels; at low arachidonic acid concentrations cyclooxygenase-2 is the major isoenzyme involved when both are present, so these drugs may selectively inhibit synthesis involving cyclooxygenase-2 because the lower flux through that pathway produces less prostaglandin G2 than the pathway involving cyclooxygenase-1, and the authors propose the class name peroxide sensitive analgesic and antipyretic drugs. 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: The apparent preference for the second enzyme may be nothing to do with binding it, and everything to do with how much peroxide each pathway makes. organism: Human and enzyme tissue_or_cell_type: Cyclooxygenase experimental_model: Review of the mechanism of paracetamol and salicylate as peroxide-sensitive inhibitors limitations: A review proposing a drug class rather than a new measurement. Its argument that apparent cyclooxygenase-2 selectivity arises from flux rather than binding is the useful part. exposure: Paracetamol and salicylate at low arachidonic acid concentrations evidence_span: {"source_cache": "artifacts/paracetamol-research/15035793.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f72415969de66bea6c0588049cbe1fd1a4b23195c0e2f5a60293eaf99a0f641e", "start_char": 0, "end_char": 1279, "text_sha256": "f72415969de66bea6c0588049cbe1fd1a4b23195c0e2f5a60293eaf99a0f641e"} [apap-p15035793] Mechanisms of action of paracetamol and related analgesics. (2003). https://pubmed.ncbi.nlm.nih.gov/15035793/ DOI: 10.1163/156856003322699573

evidence_span

{"source_cache": "artifacts/aspirin-research/26859324.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d5dab1d6b7576a909c9cef6b5c247e6a399946afbf7ef6d428d67475a363c34", "start_char": 0, "end_char": 1553, "text_sha256": "2d5dab1d6b7576a909c9cef6b5c247e6a399946afbf7ef6d428d67475a363c34"}

experimental_model

Crystal structures of an S530T murine COX-2 mutant, aspirin-acetylated human COX-2 and human COX-2 with salicylate, at 1.9 to 2.4 angstrom

exposure

Aspirin acetylation and salicylate binding, with an S530T/G533V double mutant and purification in several detergent systems

limitations

Much higher resolution than the 1995 structure and it captures salicylate separately. The authors note that detergent and lipid in the membrane-binding domain change the acetylation rate in vitro, which is a caution about all such measurements.

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

Mouse and human enzyme

plain_language

At high resolution the acetyl group seals the groove completely, and salicylate is caught sitting where aspirin sits before it reacts.

primary_references

[asa-p26859324] Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. (2016). https://pubmed.ncbi.nlm.nih.gov/26859324/ DOI: 10.1021/acs.biochem.5b01378

tissue_or_cell_type

Crystallised 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 156–167

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures of an S530T murine COX-2 mutant, aspirin-acetylated human COX-2 and human COX-2 with salicylate, at 1.9 to 2.4 angstrom · source_derived_draft · unverified_draft

### asa-acetyl-blocks-the-groove The crystal structures reveal that the acetylated Ser-530 completely blocks access to the hydrophobic groove, that the observed binding pose of salicylate is reflective of the enzyme-inhibitor complex prior to acetylation, and that the observed Thr-530 rotamer in the S530T mutant does not impede access to the groove; differential acetylation of COX-2 purified in various detergent systems and nanodiscs indicates that detergent and lipid binding within the membrane-binding domain alters the rate of the acetylation reaction in vitro. 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 high resolution the acetyl group seals the groove completely, and salicylate is caught sitting where aspirin sits before it reacts. organism: Mouse and human enzyme tissue_or_cell_type: Crystallised cyclooxygenase-2 experimental_model: Crystal structures of an S530T murine COX-2 mutant, aspirin-acetylated human COX-2 and human COX-2 with salicylate, at 1.9 to 2.4 angstrom limitations: Much higher resolution than the 1995 structure and it captures salicylate separately. The authors note that detergent and lipid in the membrane-binding domain change the acetylation rate in vitro, which is a caution about all such measurements. exposure: Aspirin acetylation and salicylate binding, with an S530T/G533V double mutant and purification in several detergent systems evidence_span: {"source_cache": "artifacts/aspirin-research/26859324.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d5dab1d6b7576a909c9cef6b5c247e6a399946afbf7ef6d428d67475a363c34", "start_char": 0, "end_char": 1553, "text_sha256": "2d5dab1d6b7576a909c9cef6b5c247e6a399946afbf7ef6d428d67475a363c34"} [asa-p26859324] Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. (2016). https://pubmed.ncbi.nlm.nih.gov/26859324/ DOI: 10.1021/acs.biochem.5b01378

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/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

{"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

availability_state

biomarker_context Imported condition classification; unverified.

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"}

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