2. Academic Validation
  3. Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling

Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling

  • Biochem Biophys Res Commun. 2020 Jun 18;527(1):90-97. doi: 10.1016/j.bbrc.2020.04.100.
Linpei Wang 1,  Anquan Li 2,  Yinhao Liu 3,  Shiyang Zhan 1,  Lei Zhong 1,  Youqin Du 3,  Dongyao Xu 1,  Wei Wang 4,  Weifeng Huang 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China.
  • 2 Department of Gastroenterology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping, 353000, Fujian, China.
  • 3 The Institute of Infection and Inflammation, Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, 443002, China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China; Clinical College of Quanzhou Medical College, Quanzhou, 362000, Fujian, China. Electronic address: [email protected].
  • 5 The Institute of Infection and Inflammation, Department of Microbiology and Immunology, Medical College, China Three Gorges University, Yichang, 443002, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, China. Electronic address: [email protected].
PMID: 32446397 DOI: 10.1016/j.bbrc.2020.04.100
Abstract

Previous studies suggest that genistein protects liver from acetaminophen (APAP)-induced injury, however, the detailed mechanism of the process is still incompletely. Therefore, present study was to investigate the potential mechanism of the genistein mediated protection against APAP-induced hepatotoxicity. As shown, supplementation with 150 mg/kg genistein greatly alleviated the increase in serum alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, hepatic malondialdehyde (MDA) contents, and reversed the decrease in hepatic GSH levels in response to overdose APAP. At the same time, hepatic SIRT1 protein and activity were markedly upregulated in mouse receiving genistein. However, the amelioration was almost abolished by the knockdown of hepatic SIRT1 expression using lentivirus carrying specific shRNA targeting SIRT1. These results were further validated by histopathology examination. Moreover, depletion of hepatic SIRT1 prevented the accumulation of Nrf2 in nucleus and the upregulation of the antioxidant gene expression in the presence of genistein and/or APAP. Concomitantly, the induced mRNA expression of UDP-glucuronosyltransferases (UGTs) by genistein was largely dependent on the SIRT1 expression and activity. Together, our results support the notion that the strong elevation of SIRT1 expression and activity may represent a potential mechanism of protection against APAP-induced liver injury by genistein.

Keywords

APAP; Genistein; Hepatotoxicity; Oxidative stress; SIRT1.

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