The effect of troxerotin combined with high intensity interval training on heart injury and expression of antioxidant genes in doxorubicin-induced cardiac toxicity in male rats

Cancers represent an important cause of morbidity and mortality, cause more than 12% of deaths in the world. Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The present study aimed to investigate the combined effect of troxerutin and high-intensity interval training (HIIT) on DOX-induced cardiac toxicity and the expression of antioxidant genes in rat hearts.

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) and Lactate dehydrogenase (LDH) changes were measured by spectrophotometry and ELISA. Expression of antioxidant genes was measured by Real-Time PCR.

DOX injection increased serum CKMB and LDH in rats in comparison to the control group (p < 0.05) and (P <0.01), respectively. HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and LDH levels (p < 0.05) and their combined effect was greater than those of individual treatments (p < 0.01). DOX injection decreased the expression of Nrf2 and Foxo1 antioxidant genes as compared with a control group (P <0.01). HIIT exercise and troxerutin consumption alone increased the expression of the Foxo1 gene as compared with the DOX group (P <0.05) and their combined effect was greater than either alone (P <0.01). HIIT exercise and troxergotTroxerutin consumption alone increased the expression of the Nrf2 gene insignificantly, but their combined effect was significantly increased (P <0.01).

The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent DOX-induced cardiac toxicity and increase the expression of antioxidant genes in rat hearts.