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.