Yijing Su and Yun Zhang contributed equally to this work.
Lipopolysaccharide exposure augments isoniazide-induced liver injury
Article first published online: 6 FEB 2014
Copyright © 2014 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 34, Issue 12, pages 1436–1442, December 2014
How to Cite
2014), Lipopolysaccharide exposure augments isoniazide-induced liver injury, J. Appl. Toxicol., 34, pages 1436–1442, doi: 10.1002/jat.2979, , , , , , and (
- Issue published online: 20 OCT 2014
- Article first published online: 6 FEB 2014
- Manuscript Revised: 25 NOV 2013
- Manuscript Accepted: 25 NOV 2013
- Manuscript Received: 11 MAR 2013
- National Natural Science Foundation of China. Grant Number: 81273604
- 111 Project. Grant Number: 111-2-07
- 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education and the Specific Fund for Public Interest Research of Traditional Chinese Medicine, Ministry of Finance. Grant Number: 200707008
- Idiosyncratic drug-induced liver injury;
Isoniazide (INH) is a classic antituberculosis drug associated with clinical idiosyncratic drug-induced liver injury. It has been hypothesized that the interaction between a drug and modest inflammation results in a decreased threshold for drug toxicity. In this study, we tested the hypothesis that INH causes liver injury in rats when coadministered with lipopolysaccharide (LPS). Neither INH nor LPS alone caused liver injury. The coadministration of INH and LPS was associated with increases in serum and histopathological markers of liver injury. Tumour necrosis factor-α expression was significantly increased in the coadministered group. The downregulation of the bile acid transporter, bile salt export pump, and multidrug resistance protein 2 at both mRNA and protein levels was observed. Furthermore, the level of Farnesoid X receptor, which regulates the bile salt export pump and multidrug resistance protein 2, were clearly decreased. These results indicate that the coadministration of nontoxic doses of LPS and INH causes liver injury; the disruption of biliary excretion is considered the primary inflammation-related characteristic of INH-induced hepatotoxicity. Copyright © 2014 John Wiley & Sons, Ltd.