Creatine and Resistance Training: A Combined Approach to Attenuate Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX), a potent chemotherapy agent, useful in the treatment of solid tumors, lymphomas, and leukemias, is limited by its potentially lethal cardiotoxicity. However, exercise has been consistently shown to mitigate the side effects of DOX, including cardiotoxicity. To date, most studies examining the relationship between exercise and DOX-induced cardiotoxicity have focused on aerobic exercise, with very few examining the role of anerobic activity. Therefore, this investigation explored the potential of creatine (CR) and resistance training (RT) in preserving cardiac health during DOX therapy. Male Sprague-Dawley rats were grouped into RT, RT + CR, sedentary (SED), and SED + CR, with each division further branching into saline (SAL) or DOX-treated subsets post-10 weeks of RT or SED activity. RT comprised progressive training utilizing specialized cages for bipedal stance feeding. CR-treated groups ingested water mixed with 1% CR monohydrate and 5% dextrose, while control animals received 5% dextrose. At week 10, DOX was administered (2 mg/kg/week) over 4-weeks to an 8 mg/kg cumulative dose. Cardiac function post-DOX treatment was assessed via transthoracic echocardiography. Left ventricular diameter during diastole was lower in DOX + CR, RT + DOX, and RT + CR + DOX compared to SED + DOX (