Apelin-13 Alleviates Hexavalent Chromium-Induced Myocardial Injury by Inhibiting ROS-mediated Oxidative Damage and Regulating Multiple Signals

Abstract

Hexavalent chromium (Cr (VI)) from environmental pollution shows severe toxicity towards human organs by causing oxidative damage. Apelin-13 may inhibit oxidative damage by blocking ROS accumulation and regulating multiple signals. However, whether apelin-13 can attenuate Cr (VI)-induced toxicity has not been explored. Herein, the protective effect and molecular mechanism of apelin-13 against K2Cr2O7-induced cardiotoxicity in vitro and in vivo were evaluated. Results show that apelin-13 significantly inhibited K2Cr2O7-induced H9c2 cytotoxicity and apoptosis, followed by the attenuated PARP cleavage and caspase activation. Further investigation revealed that apelin-13 co-treatment effectively suppressed K2Cr2O7-induced oxidative damage by inhibiting ROS accumulation. Moreover, apelin-13 co-treatment dramatically normalized MAPKs and PI3K/AKT pathways in K2Cr2O7-treated H9c2 cells. Importantly, apelin-13 administration in vivo effectively attenuated myocardial fibrosis, improved angiogenesis, and inhibited myocardial abnormal proliferation and apoptosis. Ultimately, it alleviated K2Cr2O7-induced myocardial injury in rats. Taken together, our findings validated the strategy of the use of apelin-13 to effectively combat Cr (VI)-induced myocardial injury.