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Molecules 2017, 22(4), 524; doi:10.3390/molecules22040524

Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats

State Key Laboratory of Active Substances Discovery and Drug Ability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
These authors contribute equally to this work.
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Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 9 January 2017 / Revised: 20 March 2017 / Accepted: 20 March 2017 / Published: 7 April 2017
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Abstract

The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF) were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats. View Full-Text
Keywords: bicyclol; isoniazid; rifampicin; pyrazinamide; oxidative stress; CYP2E1; cytokines; mitochondrial dysfunction; HGF bicyclol; isoniazid; rifampicin; pyrazinamide; oxidative stress; CYP2E1; cytokines; mitochondrial dysfunction; HGF
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Liu, X.; Zhao, M.; Mi, J.; Chen, H.; Sheng, L.; Li, Y. Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats. Molecules 2017, 22, 524.

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