The effect of high-intensity interval training on the expression levels of mir-149 and Sirt1, PGC1α and Nrf2 genes in doxorubicin-induced cardiac injury in rats

Abstract

In this study we have investigated the effect of HIIT on DOX-induced cardiotoxicity and the expression of mitochondrial biogenesis genes SIRT1, PGC1α, and Nrf2 as well as microRNA-149-5p in rat model. Methods, Male Wistar rats (250-270 g) were randomly divided in four groups, control, HIIT, DOX, and HIIT+DOX. HIIT was performed on a treadmill as seven alternative intervals of high and low intensity trainings for one hour a day for 6 weeks. After the last session of HIIT, DOX was injected i.p. to trained and time-matched control rats. After three 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-timePCR method. Results, 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 up-regulated the expression profiles of SIRT-1, PGC-1α and NRF-2 toward control values. In addition, DOX toxicity significantly increased the expression level of miR-149 comparing to control rats and HIIT reversed the expression of this miR in DOX-received rats.