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  2. MitoQ alleviates triptolide-induced cardiotoxicity via activation of p62/Nrf2 axis in H9c2 cells

MitoQ alleviates triptolide-induced cardiotoxicity via activation of p62/Nrf2 axis in H9c2 cells

  • Toxicol In Vitro. 2022 Oct 19;105487. doi: 10.1016/j.tiv.2022.105487.
Guoyao Tan 1 Zhiyan Qin 1 Shiqin Jiang 1 Lei Zhang 1 Gengyi Zhang 1 Min Huang 1 Zhiying Huang 1 Jing Jin 2
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: jinjing@mail.sysu.edu.cn.
Abstract

Triptolide (TP) is one of the major components of Tripterygium wilfordii, which is a traditional Chinese medicine widely used in the treatment of various autoimmune and inflammatory diseases. However, the cardiotoxicity induced by TP greatly limits its widespread clinical application. In view of the role of ROS-mediated oxidative stress in TP-induced cardiotoxicity, mitoQ, a mitochondria-targeted ROS scavenger, was used in this study to investigate its protective effect against TP-induced cardiomyocyte toxicity and its possible underlying mechanism. Here we demonstrated that mitoQ could significantly attenuate TP-induced cardiotoxicity in cardiomyocyte H9c2 cells, with a remarkable improvement in cell viability and reduction in ROS levels. P62-Nrf2 signaling pathway has been reported to play a critical role in regulating oxidative stress and protecting cells from harmful stimuli. In this study, we found that mitoQ significantly activated p62-Nrf2 signaling pathway in H9c2 cells with or without TP treatment. Moreover, knockdown of p62 or Nrf2 could block the protective effect of mitoQ against TP in H9c2 cells. Taken together, our study demonstrates that mitoQ can alleviate TP-induced cardiotoxicity via the activation of p62-Nrf2 signaling pathway, which provides new potential strategies to combat TP-induced cardiomyocyte toxicity.

Keywords

Cardiotoxicity; MitoQ; Nrf2; Oxidative stress; Triptolide; p62.

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