Quercetin attenuates NLRP3 inflammasome activation and apoptosis to protect INH-induced liver injury via regulating SIRT1 pathway.

Severe hepatotoxicity greatly limits the clinical application of the first-line anti-tuberculosis drug isoniazid(INH). Quercetin(Que) has multiple pharmacological properties, and is regarded as a potential protective agent against a variety of organ injuries. However, the exact effect of quercetin on INH-induced hepatotoxicity and the underlying mechanisms are not yet completely understood. In this study, liver injury models were established in rats and L02 cells toreveal the protective effect of Que on INH-induced hepatotoxicity and the relevant mechanism. The in vivo results indicated that Que pretreatment reduced the level of ALT/AST, improved the liver histopathological changes and substantially mitigated apoptosis in rats. In vitro, it evidently relieved INH-induced cell viability loss and apoptosis in L02 cells. Furthermore, thestudiesonmechanisms elucidated that Que remarkably elevated the expression of SIRT1 and suppressed NLRP3 inflammasome activation. Meanwhile, Que significantly inhibited the level of tumor suppressor P53, Bax, cleaved-cas3 expressionl and increased Bcl-2 expression to reduce apoptosis in vivo and in vitro. However, SIRT1 inhibitor EX527 reversed the suppression of Que on NLRP3 inflammasome activation and the protection of Que on rat liver injury and cell apoptosis. In short, our findings showed that Que exhibited protective effects against INH-induced liver damage via inhibiting the activation of NLRP3 inflammasome and apoptosis in a SIRT-dependent manner. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Yueming Zhang, Xiaoyu Qu, Huan Gao, Jinghui Zhai, Lina Tao, Jingmeng Sun, Yanqing Song, Jie Zhang. Quercetin attenuates NLRP3 inflammasome activation and apoptosis to protect INH-induced liver injury via regulating SIRT1 pathway. International immunopharmacology. 2020 Aug;85:106634

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PMID: 32492628

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