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Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway
Author(s) -
Zhang Yueming,
Zhang Wenrui,
Tao Lina,
Zhai Jinghui,
Gao Huan,
Song Yanqing,
Qu Xiaoyu
Publication year - 2019
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22369
Subject(s) - mapk/erk pathway , apoptosis , pharmacology , chemistry , quercetin , phosphorylation , viability assay , kinase , sirtuin 1 , superoxide dismutase , signal transduction , antioxidant , biochemistry , microbiology and biotechnology , downregulation and upregulation , biology , gene
Isoniazid (INH) is one of the most commonly used antituberculosis drugs, but its clinical applications have been limited by severe hepatic toxicity. Quercetin (Que), a natural flavonoid, has been proved to have many medicinal properties. This study aimed to clarify the possible protective effects of Que against INH‐induced hepatotoxicity using HepG2 cells. Our results indicated that Que significantly increased cell viability, superoxide dismutase, and GSH levels, while decreased alanine aminotransferase/aspartate aminotransferase levels. Besides, Que significantly abrogated INH‐induced cell apoptosis by upregulating the expression levels of Bcl‐2 and decreasing the levels of Bax, cleaved caspase‐3, and cleaved caspase‐9. Furthermore, Que obviously reversed the inhibition of INH on Sirtuin 1 (SIRT1) expression and extracellular signal‐regulated kinase (ERK) phosphorylation. Next, the SIRT1 inhibitor EX527 blocked the enhancement of Que upon ERK phosphorylation. Notably, EX527 partially abolished the beneficial effects of Que. In brief, our results provided the first evidence that Que protected against INH‐induced HepG2 cells by regulating the SIRT1/ERK pathway.