AUTHOR=Lv Linyan , Chang Yajie , Li Yanqing , Chen Haicheng , Yao Jiahui , Xie Yun , Liang Xiaoyan , Yang Xing , Zhang Min , Liu Guihua 

TITLE=Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.616803

DOI=10.3389/fphar.2021.616803

ISSN=1663-9812

ABSTRACT=Triptolide is widely used in clinic treatment of various diseases. Side effects including reproductive toxicity to male patients limit its application. However no detailed mechanisms or potential intervention targets have been reported. In this study, we had shown that triptolide activated mitochondrial apoptosis pathway in rat testicular leydig cells and induced cell apoptosis both in vivo and in vitro, which may cause hypoleydigism and damage spermatogenesis. Mechanically, triptolide induced dynamin-related protein 1 (Drp1) over-expression, which interfered mitochondrial dynamic stability to activate mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, could partly reverse mitochondrial dynamic disturbance and rat testicular leydig cells’ apoptosis induced by triptolide. Inhibiting Drp1 over-activation  may be a new strategy for mitigating the reproductive toxicity of triptolide.