Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells. (5th October 2015)

• Record Type: Journal Article
• Authors: Hu, Jie; Yu, Qinwei; Zhao, Fang; Ji, Jinzi; Jiang, Zhenzhou; Chen, Xin; Gao, Peng; Ren, Yuran; Shao, Shuai; Zhang, Luyong; Yan, Ming
• Is Part Of: Chemico-biological interactions. Volume 240(2015)
• Page Start: 38
• Page End: 46
• Publication Date: 2015-10-05
• Subjects: Triptolide -- Oxidative stress -- Nrf2 -- Quercetin -- Apoptosis -- Leydig cells; TP Triptolide -- Que Quercetin -- ΔΨm mitochondrial membrane potential -- GPx glutathione peroxidase -- SOD superoxide dismutase -- ROS reactive oxygen species -- Nrf2 NF-E2-related factor -- Cyt-C cytochrome C -- JNK c-Jun Nterminal kinase; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.08.004
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Triptolide (TP) is a diterpene triepoxide with variety biological activities, such as anti-inflammatory, anti-cancerogenic, immunomodulatory and pro-apoptotic activities. However, its clinical application was limited by potential toxicity. Quercetin (Que) is a member of flavonoids with anti-oxidant effects. In this study, we aimed to demonstrate the protective effect of Que in TP-induced oxidative stress and decrease of testosterone generation in reproductive damage. Leydig cells were treated with TP (20, 40 and 60 nM), which caused obvious oxidative stress increasing intracellular ROS, decreasing activities and expressions of GPx and SOD. Apoptosis was resulted from depolarization of mitochondrial membrane potential (ΔΨm) and release of cytochrome C (Cyt-C) showing increase of BAX/Bcl-2 ratio, caspase-3 and caspase-9. Treatment of Que (5 μM) prior to triptolide could restore all the TP-induced alteration in a certain dose range indicating that the oxidative stress might be one reason of TP-induced reproductive toxic effect. These results suggest that the compatibility with Que might reduce the TP-induced reproductive toxicity, which provide a probability to extend the usage of TP. Graphical abstract: Highlights: Triptolide induced oxidative stress in Leydig cells accounts for its reproductive toxicity. Protective effect of Quercetin on oxidative stress and apoptosis induced by triptolide. Mitochondria played a critical role in triptolide induced Leydig cell apoptosis.