Quercetin Reduces Oxidative Stress and Apoptosis by Inhibiting HMGB1 and Its Translocation, Thereby Alleviating Liver Injury in ACLF Rats.

Peng Fang,Bo Dou,Chongyang Ma,Jiajun Liang,Weixin Hou,Qiuyun Zhang,Omayma Eldahshan

doi:10.1155/2021/2898995

Abstract

Background Acute on chronic liver failure (ACLF) is a syndrome of acute liver failure that occurs on the basis of chronic liver disease, which is characterized by a rapid deterioration in a short period and high mortality. High mobility group box 1 (HMGB1) may be involved in the pathological process of ACLF; its specific role remains to be further elucidated. Our previous studies have shown that quercetin (Que) exerts anti-oxidant and anti-apoptotic effects by inhibiting HMGB1 in vitro. The present study aimed to investigate the effect of Que on liver injury in ACLF rats. Methods The contents of ALT, AST, TBiL, and PT time of rats in each group were observed. HE staining was used to detect liver pathology. The levels of oxidative stress indicators such as MDA, GSH, and 4-HNE in the rat liver were detected. TUNEL assay was used to detect apoptosis in rat hepatocytes. Immunofluorescence and western blot analysis were performed to explore the protective effect of Que on ACLF rats and the underlying mechanism. Results The results showed that Que could reduce the increase of serum biochemical indices, improve liver pathology, and reduce liver damage in ACLF rats. Further results confirmed that Que reduced the occurrence of oxidative stress and apoptosis of hepatocytes, and these reactions may aggravate the progress of ACLF. Meanwhile, the results of immunofluorescence and western blotting also confirmed that the expression of HMGB1 and extranuclear translocation in ACLF rat hepatocytes were significantly increased, which was alleviated by the treatment of Que. In addition, when cotreated with glycyrrhizin (Gly), an inhibitor of HMGB1, the inhibition of Que on HMGB1 and its translocation, apoptosis and oxidative stress, and the related proteins of HMGB1-mediated cellular pathway have been significantly enhanced. Conclusion Thus, Que alleviates liver injury in ACLF rats, and its mechanism may be related to oxidative stress and apoptosis caused by HMGB1 and its translocation.

Highlights

Acute on chronic liver failure (ACLF) refers to a syndrome of liver failure caused by various factors on the basis of chronic liver disease, which is manifested by acute jaundice deepening and coagulopathy [1]
hematoxylin and eosin (H&E) staining was performed to verify the extent of liver injury
What’s more, when compared with Que-100, the ALT, AST, total bilirubin (TBiL), and Prothrombin times (PTs) were further decreased after addition with Gly, an inhibitor of High mobility group box 1 (HMGB1), and the amelioration of pathologies showed the same performance

Summary

Introduction

Acute on chronic liver failure (ACLF) refers to a syndrome of liver failure caused by various factors on the basis of chronic liver disease, which is manifested by acute jaundice deepening and coagulopathy [1]. It can be complicated by various symptoms such as hepatic encephalopathy, ascites, infection, and extrahepatic organ failure [2]. Acute on chronic liver failure (ACLF) is a syndrome of acute liver failure that occurs on the basis of chronic liver disease, which is characterized by a rapid deterioration in a short period and high mortality.

Methods

Results

Conclusion