L. Polysaccharide Alleviates Oxidative Stress and Protects From Acetaminophen-Induced Hepatotoxicity Activating the Nrf2-ARE Pathway

Overview

Journal Front Pharmacol

Date 2022 May 16

PMID 35571121

Authors

Kaiping Wang

Linlin Yang

Jing Zhou

Xianglin Pan

Zihao He

Junxi Liu

Yu Zhang

Affiliations

Soon will be listed here.

Abstract

The alleviation of oxidative stress is considered an effective treatment for acetaminophen (APAP)-induced acute liver injury (AILI). However, it remains unknow whether the potential antioxidant L. polysaccharide (SCLP) protects against AILI. In this study, and experiments were conducted to verify the hepatoprotective effect of SCLP against AILI and explore the potential mechanism. We found that SCLP relieved liver histopathological changes; reversed the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and reactive oxygen species (ROS); reversed the change in liver myeloperoxidase (MPO) activity; and enhanced liver antioxidant (GSH, GSH-Px, and t-SOD) levels in APAP-treated mice, thereby significantly reducing APAP-induced liver toxicity. SCLP rescued the cell viability and alleviated oxidative stress in HO-treated mouse AML12 (Alpha mouse liver 12) hepatocytes. The results of the mechanistic studies showed that SCLP upregulated nuclear factor E2 related factor (Nrf2) expression, promoted Nrf2 nuclear translocation, and enhanced the ability of Nrf2 to bind antioxidant response elements (AREs). Furthermore, SCLP activated Nrf2-ARE pathway, thus upregulating the expression of oxidative stress-related proteins heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1(NQO-1) and glutamic acid cysteine ligase catalytic subunit (GCLC). In conclusion, this study confirmed the close correlation between liver protection by SCLP upon exposure to APAP and activated of the Nrf2-ARE pathway. These findings suggest that SCLP is an attractive therapeutic candidate drug for the treatment of AILI.

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