Component
Leflunomide
Leflunomide. Species, exposure and limitations are retained in each linked claim.
1 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
Where it participates (unsigned role)
Leflunomide given 4 hours after a hepatotoxic dose of acetaminophen afforded significant protection from liver necrosis by serum alanine aminotransferase and histopathology at 8 and 24 hours, and the mechanism was not inhibition of cytochrome-P450-catalysed bioactivation or suppression of innate immunity but inhibition of acetaminophen-induced phosphorylation of c-Jun N-terminal protein kinase, preventing downstream Bcl-2 and Bcl-XL inactivation and protecting from mitochondrial permeabilization and cytochrome c release, while also preventing induction of inducible nitric oxide synthase and formation of peroxynitrite; protection was still obtained when given 8 hours after the dose.
Experimental context and source evidence
- availability_state
- biomarker_context Imported condition classification; unverified.
- evidence_span
- {"source_cache": "artifacts/paracetamol-research/17366662.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c7eb70728aa75fa3ac54f70703ce08d7a540b3a2a7da7e4797f27a6b1312dbb", "start_char": 0, "end_char": 1791, "text_sha256": "7c7eb70728aa75fa3ac54f70703ce08d7a540b3a2a7da7e4797f27a6b1312dbb"}
- experimental_model
- Male C57BL/6 mice given a hepatotoxic dose followed by leflunomide at 4 or 8 hours
- exposure
- 750 milligrams per kilogram acetaminophen intraperitoneally, rescued with 30 milligrams per kilogram leflunomide
- limitations
- A rescue given hours after the dose, which separates the injury pathway from the bioactivation step. A mouse model at a dose far above therapeutic.
- 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
- Mouse
- plain_language
- The damage is done by a signalling kinase hours later, not by the chemistry of the metabolite alone, which is why a late rescue works.
- primary_references
- [apap-p17366662] Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury. (2007). https://pubmed.ncbi.nlm.nih.gov/17366662/ DOI: 10.1002/hep.21475
- tissue_or_cell_type
- Liver
- trigger_kind
- biomarker_context Imported condition classification; unverified.
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male C57BL/6 mice given a hepatotoxic dose followed by leflunomide at 4 or 8 hours · source_derived_draft · unverified_draft
### apap-jnk-not-bioactivation Leflunomide given 4 hours after a hepatotoxic dose of acetaminophen afforded significant protection from liver necrosis by serum alanine aminotransferase and histopathology at 8 and 24 hours, and the mechanism was not inhibition of cytochrome-P450-catalysed bioactivation or suppression of innate immunity but inhibition of acetaminophen-induced phosphorylation of c-Jun N-terminal protein kinase, preventing downstream Bcl-2 and Bcl-XL inactivation and protecting from mitochondrial permeabilization and cytochrome c release, while also preventing induction of inducible nitric oxide synthase and formation of peroxynitrite; protection was still obtained when given 8 hours after the dose. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: The damage is done by a signalling kinase hours later, not by the chemistry of the metabolite alone, which is why a late rescue works. organism: Mouse tissue_or_cell_type: Liver experimental_model: Male C57BL/6 mice given a hepatotoxic dose followed by leflunomide at 4 or 8 hours limitations: A rescue given hours after the dose, which separates the injury pathway from the bioactivation step. A mouse model at a dose far above therapeutic. exposure: 750 milligrams per kilogram acetaminophen intraperitoneally, rescued with 30 milligrams per kilogram leflunomide evidence_span: {"source_cache": "artifacts/paracetamol-research/17366662.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c7eb70728aa75fa3ac54f70703ce08d7a540b3a2a7da7e4797f27a6b1312dbb", "start_char": 0, "end_char": 1791, "text_sha256": "7c7eb70728aa75fa3ac54f70703ce08d7a540b3a2a7da7e4797f27a6b1312dbb"} [apap-p17366662] Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury. (2007). https://pubmed.ncbi.nlm.nih.gov/17366662/ DOI: 10.1002/hep.21475
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.