Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy.
basic_science · Level V
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- Record sourced from PubMed, PMID 23475203.
- Also identified by DOI 10.1038/nm.3104 and PMC identifier 3618537.
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Abstract
Co-therapy with rifampicin (RIF) and isoniazid (INH) used to treat tuberculosis in humans frequently causes liver injury. Here, using a pregnane X receptor (PXR)-humanized mouse model, we found that co-treatment with RIF and INH causes accumulation of the endogenous hepatotoxin protoporphyrin IX in the liver through PXR-mediated alteration of the heme biosynthesis pathway. These results provide insight into the mechanism of liver injury induced by co-treatment with these compounds and may lead to their safer use in the clinic.
Medical subject headings
- Antitubercular Agents
- Chemical and Drug Induced Liver Injury
- Isoniazid
- Receptors, Steroid
- Rifampin