Chlorpromazine-induced perturbations of bile acids and free fatty acids in cholestatic liver injury prevented by the Chinese herbal compound Yin-Chen-Hao-Tang.

Li Yang,Ying Xu,Xiaowen Tang,Fan Yang,Zhengtao Wang,Yinhua Xiong,Qiaoling Yang,Lili Ding

doi:10.1186/s12906-015-0627-2

Abstract

BackgroundsYin-Chen-Hao-Tang (YCHT), a commonly used as a traditional chinese medicine for liver disease. Several studies indicated that YCHT may improving hepatic triglyceride metabolism and anti-apoptotic response as well as decreasing oxidative stress .However, little is known about the role of YCHT in chlorpromazine (CPZ) –induced chlolestatic liver injury. Therefore, we aimed to facilitate the understanding of the pathogenesis of cholestatic liver injury and evaluate the effect of Yin-Chen-Hao-Tang (YCHT) on chlorpromazine (CPZ)-induced cholestatic liver injury in rats based on the change of bile acids (BAs) and free fatty acids (FFAs) alone with the biochemical indicators and histological examination.MethodsWe conducted an experiment on CPZ-induced cholestatic liver injury in Wistar rats with and without YCHT for nine consecutive days. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBIL), total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) were measured to evaluate the protective effect of YCHT against chlorpromazine (CPZ)-induced cholestatic liver injury. Histopathology of the liver tissue showed that pathological injuries were relieved after YCHT pretreatment. In addition, ultra-performance lipid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) and gas chromatography coupled with mass spectrometry (GC-MS) was applied to determine the content of bile acids, free fatty acids, respectively.ResultsObtained data showed that YCHT attenuated the effect of CPZ-induced cholestatic liver injury, which was manifested by the serum biochemical parameters and histopathology of the liver tissue. YCHT regulated the lipid levels as indicated by the reversed serum levels of TC, TG, and LDL-C. YCHT also regulated the disorder of BA and FFA metabolism by CPZ induction.ConclusionsResults indicated that YCHT exerted a protective effect on CPZ-induced cholestasis liver injury. The variance of BA and FFA concentrations can be used to evaluate the cholestatic liver injury caused by CPZ and the hepatoprotective effect of YCHT.

Highlights

Cholestasis is a prevalent form of chronic liver disease characterized as a consequence of disturbed hepatocellular secretion of bile, impaired bile formation, and slow bile flow [1]
The variance of bile acids (BAs) and free fatty acids (FFAs) concentrations can be used to evaluate the cholestatic liver injury caused by CPZ and the hepatoprotective effect of YCHT
The validated ultra-performance lipid chromatography coupled with quadrupole mass spectrometry (UPLC–MS) method based on BA and gas chromatography coupled with mass spectrometry (GC–MS) based on FFA

Summary

Introduction

Cholestasis is a prevalent form of chronic liver disease characterized as a consequence of disturbed hepatocellular secretion of bile, impaired bile formation, and slow bile flow [1]. CPZ-induced hepatotoxicity may be associated with the mechanism involving sustained activation of JNK, which leads to inflammation [4,5]. CPZ can induce cholestasis by inhibiting bile flow in vivo [6]. Previous studies on CPZinduced intrahepatic cholestasis in vitro demonstrated that the mechanismis associated with the alteration of bile acid (BA) transport receptors and oxidative stress by altering mitochondrial membrane potential and the pericanalicular distribution of F-actin [7]. Considerable amount of evidence indicates that CPZ can be used as an excellent model of drug-induced liver injury and is usually administered to mimic drug-induced cholestasis [8,9,10]. The diagnosis and assessment of the initial toxic effects of CPZ are limited and do not accurately predict cholestasis

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