Effect of high-intensity interval training on expression of microRNA-149 and genes regulating mitochondrial biogenesis in doxorubicin-cardiotoxicity in rats

We have investigated the effect of high-intensity interval exercise (HIIT) on DOX-induced cardiotoxicity and the expression of mitochondrial biogenesis genes SIRT-1, PGC-1α, and NRF-2 as well as microRNA-149-5p in a rat model. Twenty-four male Wistar rats (250–270 g) were randomly divided in four groups (n = 6/each): control, HIIT, DOX, and HIIT+DOX. HIIT was performed on a treadmill as seven alternative intervals of high and low intensity trainings for 1 h a day for 6 weeks. After the last session of HIIT, DOX was injected i.p. to trained and time-matched control rats. After 3 days, the blood and heart samples were obtained. The plasma levels of myocardial creatine kinase (CK-MB) were measured using ELISA kit. The tissue homogenates were used to determine the expression of genes and microRNA via real-time PCR method. DOX administration significantly increased CK-MB levels and reduced the expression levels of SIRT-1 and PGC-1α in comparison to control group. Prior treatment of DOX-received rats with HIIT protocol significantly reduced the CK-MB release and upregulated the expression profiles of SIRT-1, PGC-1α, and NRF-2 toward control values. In addition, DOX toxicity significantly increased the expression level of microRNA-149 comparing to control rats and HIIT reversed the expression of this microRNA in DOX-received rats. Our data suggested that DOX-induced cardiotoxicity could be, at least in part, due to impaired SIRT-1/PGC-1α/NRF-2 genes regulating mitochondrial biogenesis and microRNA-149 dysregulation. However, prior training of rats with HIIT had protective effect on DOX cardiotoxicity through reversing the expression profiles of these genes and microRNA. © 2019, Springer-Verlag London Ltd., part of Springer Nature.