Piperine Protects Against Arsenic Trioxide-Induced Cardiotoxicity in Rats: A Biochemical and Electrocardiography Study.

Abstract

Introduction: Arsenic trioxide is a highly effective chemotherapeutic agent that counteracts acute promyelocytic leukemia. However, the use of arsenic trioxide for managing acute promyelocytic leukemia has been associated with severe cardiotoxic effects. We investigated the cardioprotective effect of piperine in arsenic trioxide-induced cardiotoxicity in rats.

Methods: Cardiotoxicity was induced by administration of arsenic trioxide at 4 mg/kg body weight (bwt) orally for 30 days. The cardioprotective effect of piperine at 20 mg/kg orally was studied by cardiac biomarkers, oxidative parameters, and an electrocardiography study.

Results: Administration of arsenic trioxide at 4 mg/kg bwt orally for 30 days caused significant cardiovascular injury, confirmed by elevated cardiac enzymes CK-MB and LDH levels. Electrocardiographic (ECG) abnormalities were notable in the arsenic trioxide-treated group, such as prolonged QT and QTc intervals and reduced heart rate. There was significant myocardial oxidative impairment (TBARS increased, SOD and Catalase decreased) and inflammation (IL-6 increased).

Discussion: When piperine at 20 mg/kg was used, it decreased the CK-MB and LDH levels, reduced the prolonged QT and QTc intervals, and improved oxidative damage and inflammation.

Conclusion: This study demonstrated that piperine at 20 mg/kg orally was protective in arsenic trioxide-induced cardiotoxicity in an experimental rat model. This study is the first to combine serum biomarkers and ECG analysis to demonstrate piperine's cardioprotective role. It may have clinical relevance in exploring the potential of piperine to reduce arsenic trioxide-induced cardiotoxicity.