Resistance Training Protects against Cardiac Damage in Doxorubicin-Induced Cardiotoxicity in Rats

PURPOSE: Doxorubicin (DOX) is an effective chemotherapeutic agent that leads to a dose-dependent cardiotoxicity that may ultimately result in heart failure. This study explores whether resistance training (RT) may mitigate DOX-induced cardiac damage and examines the expression of proteins involved in muscle anabolism, catabolism, and mitochondrial dynamics in the left ventricle. METHODS: Male Sprague Dawley rats (3 months old) were divided into control (saline/sedentary, n = 10), Dox/Sed (DOX/sedentary, initial n = 16), and Dox/Tr (DOX/RT, initial n = 16) groups. DOX or saline was administered for 10 consecutive days (1 mg·kg -1 ·d -1 , i.p.), starting concomitantly with RT, which consisted of ladder climbing with tail-attached weights (15 repetitions per day; 5 d·wk -1 ; 20%-60% of maximal load; for 8 wk). Seventy-two hours after the last RT session, rats were euthanized and left ventricular fragments were dissected and processed for microscopy and Western blot. RESULTS: RT reduced the early and high mortality observed in the Dox/Sed group and prevented DOX-induced cardiac fiber atrophy and fibrosis. Cardiomyocyte ultrastructural damage, including misaligned sarcomeres, myofibril rupture, autophagosome presence, and mitochondrial damage, was mitigated by RT. While Akt, p-Akt, MuRF1, and Atrogin-1 levels in the left ventricle were similar among groups, both DOX groups displayed reduced mTOR, ERK, and p-ERK expression compared with the control group. Regarding proteins related to mitochondrial dynamics, OPA1 expression did not differ among groups, Mfn2 was significantly lower in both DOX groups compared with control, and FIS1 levels were lower only in the Dox/Tr group. In addition, Dox/Tr presented higher levels of PGC1α expression in comparison with control and Dox/Sed groups. CONCLUSIONS: RT may be valuable to protect the heart against the structural damage induced by DOX via the modulation of proteins involved in mitochondrial dynamics.