Differential toxicities of triptolide to immortalized podocytes and the podocytes in vivo

Publication date: January 2019Source: Biomedicine & Pharmacotherapy, Volume 109Author(s): Mengjie Sun, Hui Song, Yuting Ye, Qianqian Yang, Xiaodong Xu, Xiaodong Zhu, Jiong Zhang, Shaolin Shi, Jinquan Wang, Zhihong LiuAbstractTriptolide (TP) has an anti-proteinuric effect and is used for the treatment of podocytopathies. TP has also been shown to act directly on immortalized podocytes in culture to protect them from injury. In the present study, we examined the effect of TP on healthy podocytes both in vitro and in vivo to better understand the action of TP on podocytes. We found that treatment of TP at 10 ng/ml, a concentration that is routinely used for podocyte protection, was sufficient to activate pro-apoptotic signaling of MAPK p38, p53 and BAX and induced apoptosis in cultured podocytes; and higher concentrations of TP exacerbated the p38, p53 and BAX activations and apoptosis. Moreover, TP severely downregulated the genes that are essential for podocyte structure and function. Interestingly, in contrast with other agents TP-induced podocyte injury was not prevented by glucocorticoids. In vivo, high-dose TP treatment for prolonged time did not cause podocyte injury, essential genes downregulation, and proteinuria in mice. TP was also not toxic to the podocytes with isolated glomeruli ex vivo. In summary, TP is toxic to immortalized podocytes in culture but not to the podocytes in animals or isolated glomeruli ex vivo. Our study suggests that immortalized podocytes mig...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research