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Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction [Anatol J Cardiol]
Anatol J Cardiol. Ahead of Print: AJC-83710 | DOI: 10.14744/AnatolJCardiol.2019.83710  

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

Li Zhao
Department of Cardiology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

Objective. The objective of this study was to investigate the effects of trimetazidine (TMZ) and coenzyme Q10 (CoQ10) on cisplatin-induced cardiotoxicity in rat cardiomyocytes.
Methods. Rat cardiomyocytes were isolated and subjected to cisplatin (200 μM) treatment with or without TMZ (200 μM) and CoQ10 (200 mg/L) pretreatment. Cell viability, apoptosis, the oxidant and antioxidant indicators, mitochondrial dysfunction were examined.
Results. 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 treatment exerted a pronounced effect than each of these agents (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 either agent alone (p < 0.01 for ROS, MDA, CAT and cytosolic cyto-c, p < 0.05 for SOD, nuclear Nrf2, and ΔΨm loss).
Conclusion. TMZ and CoQ10 had protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.

Keywords: cisplatin-induced cardiotoxicity, trimetazidine, coenzyme Q10, oxidative stress, mitochondrial dysfunction




Corresponding Author: Li Zhao, China


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