Format

Send to

Choose Destination
Nat Med. 2013 Apr;19(4):418-20. doi: 10.1038/nm.3104. Epub 2013 Mar 10.

Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy.

Author information

1
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.

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.

PMID:
23475203
PMCID:
PMC3618537
DOI:
10.1038/nm.3104
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center