Journal
NATURE MEDICINE
Volume 19, Issue 4, Pages 418-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3104
Keywords
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [DK090305]
- National Cancer Institute Intramural Research Program
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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.
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