Protective effects of S ‐carvedilol on doxorubicin‐induced damages to human umbilical vein endothelial cells and rats

AbstractDoxorubicin (DOX) is a highly active anticancer drug with severe cytotoxicity, which is strongly associated with oxidative stress. Carvedilol (CAR), used as its racemate withS‐CAR andR‐CAR (1:1), has been previously reported to ameliorate the DOX‐induced cytotoxicity. However, the main contributor from CAR of its protective effects has not been clear. Therefore, in this study, we aimed to investigate further the different effects of CAR enantiomers on DOX‐induced cytotoxici ty in human umbilical vein endothelial cells and rats, respectively. Results indicated thatS‐CAR could significantly attenuate DOX‐induced cell death, apoptotic morphological changes, decrease the mitochondrial membrane potential and oxidative stress responses by increasing the superoxide dismutase and catalase activities, and decreasing malondialdehyde contents and reactive oxygen spe cies levels via the phosphoinositide 3‐kinase/AKT/endothelial nitric oxide synthase pathway in vitro. Consistent with the in vitro study, the protective effects ofS‐CAR on the myocardial tissues and hemodynamics were also detected in rats suffering because of DOX treatment. With the obtained results, we can first conclude thatS‐CAR provides superior protection to injury induced by DOX relative to that of racemic CAR andR‐CAR.

Source: Journal of Applied Toxicology - July 9, 2019 Category: Toxicology Authors: Ting Wu, Haixin Li, Qunsheng Lan, Ze ‐an Zhao, Ying Cao, Pingzheng Zhou, Shanhe Wan, Jiajie Zhang, Hong Jiang, Qun Zhang, Jianxin Pang Tags: RESEARCH ARTICLE Source Type: research