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

Background: The efficacy of doxorubicin (DOX) in treating numerous solid tumors has been restricted, especially due to its most serious side effect: Cardiotoxicity. Little research has been conducted on the protective benefits of high-intensity interval training (HIIT) against the cardiotoxicity caused by DOX (CTD). Objectives: The study aimed to explore the protective impact of HIIT on CTD by analyzing genes associated with the autophagy process and mitochondrial dynamics (such as Beclin1, LC3II, DRP1, FIS1, OPA1, and Mfn2). Methods: Twenty-four Wistar rats were randomly assigned into four groups (n = 6): Control, DOX (20 mg/kg body weight), HIIT (seven circles of four minutes of high-intensity exercise isolated with three minutes of moderate-intensity for eight weeks), and HIIT + DOX. The DOX treatment was completed after the last HIIT session, and tissue sampling was performed after 72 hours. RT-PCR test was employed to analyze gene expression. One-way analysis of variance and Tukey's post hoc tests were used for analyzing the data (α < 0.05). Results: The DOX injection led to a non-significant increase in mRNA levels of Drp1 and Fis1, but it significantly increased mRNA levels of OPA1 (P = 0.000). However, it also significantly decreased the mRNA levels of LC3II (P = 0.002), Beclin1 (P = 0.005), and MNF2 (P = 0.000). In addition, HIIT resulted in a significant reduction in the gene expression of FIS1 (P = 0.014), DRP1 (P = 0.000), and OPA1 (P = 0.000). Conversely, HIIT significantly led to an increase in mRNA levels of LC3II (P = 0.01) and Beclin1 (P = 0.0001). HIIT before DOX significantly decreased mRNA levels of Drp1 (P = 0.000), Fis1 (P = 0.000), and OPA1 (P = 0.000), while increasing the mRNA levels of LC3II (P = 0.000) and Beclin1 (P = 0.008). HIIT alone and before DOX also resulted in a non-significant increase in MNF2 mRNA levels. Conclusions: The HIIT appears to be an appropriate protective strategy against CTD by attenuating DOX-induced disturbances in the mitochondrial dynamics and autophagy process.