Quercetin Mitigates Cisplatin-Induced Oxidative Damage and Apoptosis in Cardiomyocytes through Nrf2/HO-1 Signaling Pathway

Shih Hao Wang, Kun Ling Tsai, Wan Ching Chou, Hui Ching Cheng, Yu Ting Huang, Hsiu Chung Ou, Yun Ching Chang

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Cisplatin is massively used to treat solid tumors. However, several severe adverse effects, such as cardiotoxicity, are obstacles to its clinical application. Cardiotoxicity may lead to congestive heart failure and even sudden cardiac death in patients receiving cisplatin. Therefore, finding a novel therapeutic strategy for the prevention of cisplatin-induced cardiotoxicity is urgent. Quercetin is a flavonol compound that can be found in dietary fruits and vegetables. The antioxidant function and anti-inflammatory capacity of quercetin have been reported. However, whether quercetin could protect against cisplatin-caused apoptosis and cellular damage in cardiomyocytes is still unclear. H9c2 cardiomyocytes were treated with cisplatin (40 μM) for 24 h to induce cellular damage with or without quercetin pretreatment. We found that quercetin activates Nrf2 and HO-1 expression, thereby mitigating cisplatin-caused cytotoxicity in H9c2 cells. Quercetin also increases SOD levels, maintains mitochondrial function, and reduces oxidative stress under cisplatin stimulation. Quercetin attenuates cisplatin-induced apoptosis and inflammation in H9c2 cardiomyocytes; however, these cytoprotective effects were diminished by silencing Nrf2 and HO-1. In conclusion, this study reports that quercetin has the potential to antagonize cisplatin-caused cardiotoxicity by reducing ROS-mediated mitochondrial damage and inflammation via the Nrf2/HO-1 and p38MAPK/NF-κBp65/IL-8 signaling pathway. This study provided the theoretical basis and experimental proof for the clinical application of quercetin as a new effective strategy to relieve chemotherapy-induced cardiotoxicity.

原文English
頁(從 - 到)1281-1298
頁數18
期刊American Journal of Chinese Medicine
50
發行號5
DOIs
出版狀態Published - 2022 5月 31

All Science Journal Classification (ASJC) codes

  • 補充和替代醫學

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