The Synergistic Effect of High-Intensity Interval Training and Troxerotin on Heart Injury and Mitochondrial Function in Doxorubicin-Induced Cardiac Toxicity

Abstract

Introduction: Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to the cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The aim of the present study was to investigate the combination effect of high-intensity interval training (HIIT) and troxerutin on DOX-induced cardiac toxicity and indices of mitochondrial function in rat hearts.

Methods: Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). The Creatine kinase (CKMB) changes was measured by spectrophotometry and ELISA. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential were measured by determining the intensity of relevant fluorescent dyes.

Results: DOX injection increased serum CKMB in rats in comparison to control group (P<0.05). HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and mitochondrial ROS levels (P<0.05) and their combined effect was greater than those of individual treatments (P<0.01). DOX injection reduced the mitochondrial membrane potential as compared with control group (P<0.01). While the effect of HIIT training or troxerutin alone were not significant on the mitochondrial membrane potential, their combined application significantly increased the mitochondrial membrane potential compared with DOX group (P<0.05).

Conclusion: The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent the DOX-induced cardiac toxicity and improve mitochondrial function in rat heart.