Calcium homeostasis and endoplasmic reticulum stress are involved in Salvianolic acid B-offered protection against cardiac toxicity of arsenic trioxide

Arsenic trioxide (ATO) is a potent anticancer agent used to treat acute promyelocytic leukemia.However, its cardiotoxicity limits ATO's widespread clinical use.Previous studies demonstrated that ATO may aggravate Ca 2+ overload and promote endoplasmic reticulum stress (ERS).Salvianolic acid B (Sal B) is cardioprotective against ATO and enhances ATO's anticancer activities.The present study assessed whether the Sal B protective effect was related to maintenance of Ca 2+ homeostasis and inhibition of ER stress.Male BALB/c mice were injected with ATO or ATO+Sal B once a day via the tail vein for 2 weeks.We then detected the effects of Sal B in real time using adult rat ventricular cardiomyocytes in vitro using an IonOptix MyoCam system.Sal B treatment alleviated ATO-induced abnormal cardiac contractions and Ca 2+ homeostasis imbalance.Sal B increased sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) activity, regulated Ca 2+ handling protein expression, and decreased expression of ERS proteins.Our results demonstrate that the cardioprotective effect of Sal B correlates with SERCA modulation, maintenance of Ca 2+ homeostasis, and inhibition of ER stress.These findings suggest Sal B may ameliorate ATO cardiotoxicity during clinical application.