Protective Effect of High-Intensity Interval Training on Doxorubicin-Induced Cardiotoxicity by Reducing MiR-499 Expression in Male Rats

Doxorubicin (DOX) is an effective chemotherapy treatment for various cancers, but its use has been restricted due to cardiotoxicity effects. Studies about the protective effect of High-Intensity Interval Training (HIIT) against DOX-induced cardiotoxicity and its mechanisms are rare. This study aimed to investigate the protective effect of HIIT against the DOX-induced cardiotoxicity on the level of miR-499 expression which is widely expressed under the physiological conditions in the cardiomyocytes.

Twenty-four male Wistar rats were randomly assigned into four groups (n=6/group) including DOX (20 mg/kg body weight), HIIT (eight weeks, and seven 4-minutes sets of intervals at 80%–90% of VO2max interspersed with 3 minutes periods at 65%–75% of VO2max), HIIT+DOX and Control groups. The mRNA expression level was determined using the RT-PCR method. One-way analysis of variance followed by Tukey's post hoc test was used for statistical analysis of data (α<0.05).

The results showed that DOX-induction significantly increased the MIR-499 expression in the left ventricular tissue of the rats’ heart (P<0.05). Also, the expression level of MIR-499 was increased after exercise, but this difference was not statistically significant. Exercise before the DOX-induction also led to a significant reduction of MIR-499 expression in the HIIT+ DOX group compared with the DOX group (P<0.05).

Therefore, performing HIIT before DOX induction can reduce the changes in MIR-499 expression caused by DOX. Therefore, HIIT could be a proper strategy for protecting the heart against DOX-induced cardiotoxicity by reducing MIR-499 expression.