Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells

• DOI: 10.1016/j.cbi.2015.08.004
• Publication Date: 2015-08-13T02:03:06Z
• Authors: Jie Hu; Qinwei Yu; Fang Zhao; Jinzi Ji; Zhenzhou Jiang; Xin Chen; Peng Gao; Yuran Ren; Shuai Shao; Luyong Zhang; Ming Yan
• Keywords: Male; 0303 health sciences; Cell Survival; Leydig Cells; Apoptosis; Phenanthrenes; Protective Agents; Polymerase Chain Reaction; Antioxidants; Rats; 3. Good health; Rats, Sprague-Dawley; Oxidative Stress; 03 medical and health sciences; Animals; Epoxy Compounds; Humans; Quercetin; Diterpenes

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.