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

Abstract

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction 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 and without TMZ (200 μM) and CoQ10 (200 mg/L) pretreatment. The cell viability, apoptosis, oxidant and antioxidant indicators, and 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 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). Conclusion: TMZ and CoQ10 showed protective effects against cisplatin-induced cardiotoxicity via attenuating oxidative stress.

Antioxidant effect of acetyl-l-carnitine against cisplatin-induced cardiotoxicity

“…Zhau studied rat cardiomyocyte cell cultures in vitro, finding that ROS and MDA levels were decreased by these agents whereas SOD-2 expression was increased compared with the effects of CDDP administration. 29 His data contract the literature and our in vivo data. A candidate protective agent such as an antioxidant is expected to reverse the increases in protein expression caused by CDDP.…”

Rosuvastatin and simvastatin attenuate cisplatin-induced cardiotoxicity via disruption of endoplasmic reticulum stress-mediated apoptotic death in rats: targeting ER-Chaperone GRP78 and Calpain-1 pathways

“…Many drug moieties have been tested to abate CP-induced cardiotoxicity; however, little achievement has been reached [ 17 ]. Statins; 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, used clinically to enhance biosynthesis of cholesterol [ 8 ].…”

Combined intake of blueberry juice and probiotics ameliorate mitochondrial dysfunction by activating SIRT1 in alcoholic fatty liver disease

“…Oxidative stress, characterized by the characteristic of ROS, increasing malondialdehyde (MDA), and the inhibition of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione (GSH) [ 26 – 28 ], is closely linked to mitochondrial function. Excessive oxidative stress can damage mitochondria, leading to mitochondrial dysfunction[ 29 ].…”