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- Title
Quercetin Mitigates Cisplatin-Induced Oxidative Damage and Apoptosis in Cardiomyocytes through Nrf2/HO-1 Signaling Pathway.
- Authors
Wang, Shih-Hao; Tsai, Kun-Ling; Chou, Wan-Ching; Cheng, Hui-Ching; Huang, Yu-Ting; Ou, Hsiu-Chung; Chang, Yun-Ching
- Abstract
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- κ Bp65/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.
- Subjects
CARDIOVASCULAR diseases risk factors; CARDIOTOXICITY; STATISTICS; MYOCARDIUM; HEART cells; NUCLEAR factor E2 related factor; ANTI-inflammatory agents; WESTERN immunoblotting; ONE-way analysis of variance; APOPTOSIS; ANTIOXIDANTS; RNA; OXIDATIVE stress; QUERCETIN; CELLULAR signal transduction; CELL survival; GENE expression; CISPLATIN; ENZYME-linked immunosorbent assay; FLUORESCENT antibody technique; DESCRIPTIVE statistics; RESEARCH funding; TUMORS; POLYMERASE chain reaction; DATA analysis; HEART failure; CYTOPLASM
- Publication
American Journal of Chinese Medicine, 2022, Vol 50, Issue 5, p1281
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X22500537