Protective Effect of Continuous Aerobic Training and Crocin on Doxorubicin-Induced Apoptosis in the Heart Tissue of Rats

Background: Doxorubicin (DOX) is widely used to treat various cancers, but its cardio-toxicity restricts its therapeutic application. Objectives: This study aimed to investigate the effect of 8 weeks of continuous aerobic training (CAT) and administration of crocin (Cr) on the apoptotic index and the expression of Bax and Bcl-2 genes on the DOX-induced cardio-toxicity of rats. Methods: In this experimental study, 50 male Wistar rats were randomly divided into 5 groups, including control, DOX, DOX + CAT, DOX + Cr, and DOX + CAT + Cr groups. Continuous aerobic training consisted of 60 minutes of running with the intensity of 40% - 60% of maximum speed (5 days/week). Apoptotic index and the expression levels of Bax and Bcl-2 genes were determined in the heart tissue. Results: Doxorubicin significantly increased Bax gene expression in the heart tissue of animals (P < 0.001). In contrast, Bcl-2 gene expression significantly decreased (P < 0.001). In all experimental groups, the Bax/Bcl-2 ratio and the percentage of the terminal deoxynucleotidal transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells were significantly diminished compared to the DOX-intoxicated animals. Among experimental groups, CAT had more antiapoptotic effects against DOX-induced cardiac toxicity. Conclusions: Continuous aerobic training and Cr, alone or in combination, could attenuate DOX-induced cardiotoxicity by suppressing apoptosis in the rats.