Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy

Rifampicin and isoniazid co–therapy frequently causes liver injury in humans. A pregnane X receptor–humanized mouse model revealed that rifampicin and isoniazid co–treatment causes accumulation of protoporphyrin IX, an endogenous hepatotoxin, in the liver via a pregnane X receptor–mediated alteratio...

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Autores principales: Li, Feng, Lu, Jie, Cheng, Jie, Wang, Laiyou, Matsubara, Tsutomu, Csanaky, Iván L., Klaassen, Curtis D., Gonzalez, Frank J., Ma, Xiaochao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618537/
https://www.ncbi.nlm.nih.gov/pubmed/23475203
http://dx.doi.org/10.1038/nm.3104
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author Li, Feng
Lu, Jie
Cheng, Jie
Wang, Laiyou
Matsubara, Tsutomu
Csanaky, Iván L.
Klaassen, Curtis D.
Gonzalez, Frank J.
Ma, Xiaochao
author_facet Li, Feng
Lu, Jie
Cheng, Jie
Wang, Laiyou
Matsubara, Tsutomu
Csanaky, Iván L.
Klaassen, Curtis D.
Gonzalez, Frank J.
Ma, Xiaochao
author_sort Li, Feng
collection PubMed
description Rifampicin and isoniazid co–therapy frequently causes liver injury in humans. A pregnane X receptor–humanized mouse model revealed that rifampicin and isoniazid co–treatment causes accumulation of protoporphyrin IX, an endogenous hepatotoxin, in the liver via a pregnane X receptor–mediated alteration of heme biosynthesis pathway. These results provide novel insight into the mechanism of rifampicin and isoniazid–induced liver injury that may be applied to clinical management of the hepatotoxicity associated with tuberculosis chemotherapy.
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spelling pubmed-36185372013-10-01 Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy Li, Feng Lu, Jie Cheng, Jie Wang, Laiyou Matsubara, Tsutomu Csanaky, Iván L. Klaassen, Curtis D. Gonzalez, Frank J. Ma, Xiaochao Nat Med Article Rifampicin and isoniazid co–therapy frequently causes liver injury in humans. A pregnane X receptor–humanized mouse model revealed that rifampicin and isoniazid co–treatment causes accumulation of protoporphyrin IX, an endogenous hepatotoxin, in the liver via a pregnane X receptor–mediated alteration of heme biosynthesis pathway. These results provide novel insight into the mechanism of rifampicin and isoniazid–induced liver injury that may be applied to clinical management of the hepatotoxicity associated with tuberculosis chemotherapy. 2013-03-10 2013-04 /pmc/articles/PMC3618537/ /pubmed/23475203 http://dx.doi.org/10.1038/nm.3104 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Li, Feng
Lu, Jie
Cheng, Jie
Wang, Laiyou
Matsubara, Tsutomu
Csanaky, Iván L.
Klaassen, Curtis D.
Gonzalez, Frank J.
Ma, Xiaochao
Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
title Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
title_full Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
title_fullStr Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
title_full_unstemmed Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
title_short Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
title_sort human pxr modulates hepatotoxicity associated with rifampicin and isoniazid co–therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618537/
https://www.ncbi.nlm.nih.gov/pubmed/23475203
http://dx.doi.org/10.1038/nm.3104
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