期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 240, 期 -, 页码 38-46出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2015.08.004
关键词
Triptolide; Oxidative stress; Nrf2; Quercetin; Apoptosis; Leydig cells
资金
- Major Scientific and Technological Special Project for Significant New Drugs Creation [2012ZX09504001-001]
- National Natural Science Foundation of China [81102876, 81430082]
- Fundamental Research Funds for the Central Universities [ZL15005, YD2014SK0002]
- 333 high level project of Jiangsu Province
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 (Delta Psi m) and release of cytochrome C (Cyt-C) showing increase of BAX/BcI-2 ratio, caspase-3 and caspase-9. Treatment of Que (5 mu M) 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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