High-Intensity Interval Training Protectively Modulates Doxorubicin- Induced Changes in Cardiac Mitochondrial Dynamics and Autophagy Process

Purpose Clinical use of doxorubicin (DOX) in cancer treatment is limited due to the most serious cardiotoxicity side effects. Limited studies have been conducted on the protective effects of high-intensity interval training (HIIT) on DOX-induced cardiotoxicity (DCT). The study aimed to explore the protective impact of HIIT on DCT by analyzing genes associated with the autophagy process and mitochondrial dynamics (such as Beclin1, LC3II, DRP1, FIS1, OPA1, and MFN2). Methods Wistar rats (N = 24) were randomly divided into Control, DOX (20 mg/kg body weight), HIIT (8 weeks, 7 sets of 4 minutes 80–90% VO2max isolated with 3-minute periods of 65–75% VO2max) and 4), and HIIT + DOX groups. DOX treatment was completed after the last session of HIIT, and the left ventricular tissue was harvested 72 hours after it. Gene expression assessment was done using the RT-PCR test. The data were analyzed by one-way analysis of variance with Tukey's post hoc test (α < 0.05). Results DOX induction non-significantly increased Drp1 and Fis1 mRNA levels (p < 0.05). It also significantly decreases LC3II, Beclin1, and MNF2 mRNA levels and increases OPA1 mRNA levels (p < 0.05). Also, HIIT per se and before DOX induction not only significantly decreased Drp1, Fis1, and OPA1 mRNA levels but also led to an increase in LC3II and Beclin1 mRNA levels. HIIT per se and before DOX induction also non-significantly increased MNF2 mRNA level (p < 0.05). Conclusion Therefore, HIIT appears to be an appropriate protective strategy against DCT by attenuating the DOX-induced disturbances in the mitochondrial dynamics and autophagy process.