Investigate the combination effect of Troxerotin and high-intensity interval training on expression of mitophagy genes Mfn2 and Parkin and Doxorubicin-induced cardiotoxicity in rat cardiac cells

Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to the cardiac toxicity. The present study aimed to investigate the combination effect of troxerutin (TRX; It is derived from the flavonoid rutin and has pharmacological properties) and high-intensity interval training (HIIT) on DOX-induced cardiotoxicity and expression of mitophagy genes Mfn2 and Parkin in rat cardiac cells.

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). To confirm the induction of doxorubicin cardiotoxicity, it was shown that DOX injection increased serum level of lactate dehydogenase from 57±3 U/l to 171±6 U/l. The expression of mitophagy genes including Mfn2 and Parkin was measured by Real-Time PCR.

DOX injection decreased the expression of mitophagy genes Mfn2 and Parkin (P<0.01). The combined effect of HIIT exercise and troxerutine consumption led to a significant increase in the expression of mitophagy genes Mfn2 (P<0.05) and Parkin (P<0.01) compared to the DOX group.

The combined application of HIIT exercise and troxerutin can increase the expression of mitophagy genes Mfn2 and Parkin in cardiac cells of DOX-receiving rats and reduce DOX-induced cardiac toxicity.