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

• Published in: Anatolian journal of cardiology Vol. 22; no. 5; pp. 232 - 239
• Main Author: Zhao, Li
• Format: Journal Article
• Language: English
• Published: Turkey Kare Publishing 01-11-2019; KARE Publishing
• Subjects: Animals; Antioxidants - pharmacology; Apoptosis - drug effects; Cardiotoxicity - prevention & control; Cell Survival - drug effects; Cisplatin - adverse effects; cisplatin-induced cardiotoxicity; coenzyme q10; Drug Therapy, Combination; Mitochondria - drug effects; mitochondrial dysfunction; Myocytes, Cardiac - drug effects; Original Investigation; oxidative stress; Rats; trimetazidine; Trimetazidine - pharmacology; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology
• ISSN: 2149-2263; 2149-2271; 2149-2263
• DOI: 10.14744/AnatolJCardiol.2019.83710

The objective of this study was to investigate the effects of trimetazidine (TMZ) and coenzyme Q10 (CoQ10) on cisplatin-induced cardiotoxicity in rat cardiomyocytes.
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.
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).
TMZ and CoQ10 showed protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.