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

Xin Liu,Manman Zhao,Yan Li,Jiaqi Mi,Hui Chen,Li Sheng

doi:10.3390/molecules22040524

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.

Highlights

Tuberculosis (TB), an airborne infectious disease, is one of the major public health issues in the world, especially in developing countries
Anti-TB drug-induced liver injury was indicated by the elevation of serum alanine
AUC0−tinhibition was significantly prevented by decrease the co-administration bicyclol. These results indicated thatofCYP2E1 affected prevented by the co-administration of bicyclol

Summary

Introduction

Tuberculosis (TB), an airborne infectious disease, is one of the major public health issues in the world, especially in developing countries. Isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) are first-line drugs for anti-TB chemotherapy. The hepatotoxicity caused by these drugs is a major concern for clinical treatment due to the long therapy duration and concurrent use of several medications [2]. The mechanism of liver damage induced by the regimen comprised of INH, RIF, and PZA was partially characterized. Toxic intermediaries and reactive oxygen species (ROS) derived from INH biotransformation have been implicated in the progression of hepatotoxicity [3,4]. INH is known to be directly or indirectly metabolized to the toxic metabolites (acetylhydrazine and hydrazine) by N-acetyltransferase and amidohydrolase in the liver [5,6,7].

Objectives

Methods

Results

Conclusion