Effects of Ethyl Pyruvate on Bile Duct Ligation-Induced Liver Fibrosis by Regulating Nrf2 Pathway and Proinflammatory Cytokines in Rats.

Yonghua Zong,Wenqian Qi,Shuai Li,Mingxiao Zhang,Chen Lu,Tonghua Liu,Huijun Yang,Xiaosong Hu,Juan Li

doi:10.1155/2019/2969802

Abstract

Aim The aim of this paper is to investigate the effects of ethyl pyruvate (EP) on experimental liver fibrosis induced by bile duct ligation (BDL) and explore the underlying molecular mechanisms. Material and Method Rats were randomly divided into three groups: the sham group, the BDL group, and the BDL+EP group. Liver fibrosis was induced by common bile duct ligation and was evaluated by serum biochemical parameter levels, Masson's trichrome staining, α-SMA expression, and collagen I deposition. The levels of Nrf2 signaling pathway-related antioxidant genes (Nrf2, SOD2, NQO1, and GSH-Px) in liver tissues were also measured. Meanwhile, the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27 were analyzed. In BDL-induced liver fibrosis rats, the successfully established model was confirmed by the significant increase of serum ALT and AST levels, the high liver fibrosis score, α-SMA expression, and collagen deposition. Results Compared with the BDL group, EP administration could diminish fibrosis level and substantially increase the expression of Nrf2 signaling pathway-related antioxidant genes. Furthermore, EP significantly suppressed the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27. Conclusions The results suggested that EP administration could effectively inhibit the liver fibrosis induced by BDL in rat, which may be associated with the enhanced activity of Nrf2 to mediate antioxidant enzyme system and downregulate the inflammatory genes.

Highlights

Liver fibrosis is a common result of repeated hepatic injury, which is characterized by the deposition of extracellular matrix (ECM)
The liver fibrosis score was lower in the BDP+ethyl pyruvate (EP) group at 2 and 4 weeks compared with the bile duct ligation (BDL) group (Figure 1(c), P < 0:01)
The present study demonstrated that EP could inhibit the liver fibrosis progression in rats, which was indicated by the improvements of serum ALT and AST levels and liver fibrosis contents

Summary

Introduction

Liver fibrosis is a common result of repeated hepatic injury, which is characterized by the deposition of extracellular matrix (ECM). Activated hepatic stellate cells (HSCs) are the major sources of myofibroblasts and the main ECMproducing cells in the fibrogenic process [1,2,3,4]. Reactive oxygen species (ROS) has been confirmed as a key step in onset and progression of liver fibrosis [5], which causes excessive damage to hepatocytes and significantly leads to HSC activation [6, 7]. Previous studies suggested that ROS contributed to HSC activation via mediating cytokine. It was reported that superoxide anion (O2-), acetaldehyde, and arachidonic acid could stimulate HSCs. ROS could promote early growth response factor-1 expression on protein and mRNA levels, which was a promoter of inflammation in cholestatic liver fibrosis

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