Swimming training attenuates doxorubicin induced cardiomyopathy by targeting the mir-17-3p/KEAP1/NRF2 axis

Doxorubicin (DOX), as a first-line anticancer drug, is widely used in the treatment of various cancers. However, its clinical application is restricted due to its severe cardiac toxicity. Previous studies have indicated exercise training can alleviate the DOX-induced cardiotoxicity (DIC), but the underlying mechanism remains unclear. Our research has discovered, post-exercise, an elevated expression level of mir-17-3p, but in DIC its level decreases. Therefore, we further studied the effect of exercise mir-17-3p axis on DIC. In vivo, we simulated DIC mouse model, followed by an intervention using swimming and adenovirus to inhibit mir-17-3p. We found that inhibition of mir-17-3p can weaken the protection of exercise against DIC, presenting as weakened heart function. Besides, the levels of Malondialdehyde and Fe