Genistein protects against acetaminophen-induced liver toxicity through augmentation of SIRT1 with induction of Nrf2 signalling
| Autor: | Lei Zhong, Youqin Du, Anquan Li, Wei Wang, Shiyang Zhan, Dong-yao Xu, Linpei Wang, Yinhao Liu, Weifeng Huang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male NF-E2-Related Factor 2 Biophysics Genistein Pharmacology medicine.disease_cause Protective Agents Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Sirtuin 1 medicine Animals Molecular Biology Acetaminophen Liver injury Gene knockdown digestive oral and skin physiology food and beverages Cell Biology Glutathione Analgesics Non-Narcotic medicine.disease Malondialdehyde Mice Inbred C57BL 030104 developmental biology chemistry Liver 030220 oncology & carcinogenesis Chemical and Drug Induced Liver Injury Oxidative stress medicine.drug Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 527(1) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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