Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

TMZ and CoQ10 showed protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.

Rat cardiomyocytes were isolated and subjected to cisplatin (200 μM) treatment with and without TMZ (200 μM) and CoQ10 (200 mg/L) pretreatment. The cell viability, apoptosis, oxidant and antioxidant indicators, and mitochondrial dysfunction were examined.

The objective of this study was to investigate the effects of trimetazidine (TMZ) and coenzyme Q10 (CoQ10) on cisplatin-induced cardiotoxicity in rat cardiomyocytes.

TMZ or CoQ10 significantly attenuated cisplatin-induced cell viability inhibition (p<0.01) and apoptosis (p<0.001), and the combined use of TMZ and CoQ10 pretreatment exerted a pronounced effect compared to the effects of using each of these agents individually (p<0.05). TMZ or CoQ10 inhibited the levels of reactive oxidative species (ROS, p<0.01) and malondialdehyde (MDA, p<0.001 and p<0.01, respectively), elevated the activities of antioxidant enzymes superoxide dismutase (SOD, p<0.01) and catalase (CAT, p<0.01 and p<0.05, respectively), evidently enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2, p<0.05), alleviated mitochondrial membrane potential (ΔΨm) loss (p<0.05), and down-regulated the release of cytochrome c (cyto-c) into the cytosol (p<0.01) in cisplatin-treated cells. The combined use of TMZ and CoQ10 treatment was more effective than using either agent alone (p<0.01 for ROS, MDA, CAT, and cytosolic cyto-c; p<0.05 for SOD, nuclear Nrf2, and ΔΨm loss).