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

ZHAO, Li

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 (Fudan Üniversitesi, Kardiyoloji Bölümü, Kadın Hastalıkları ve Doğum Hastanesi, Şangay, Çin)

The Anatolian Journal of Cardiology

1 0

Yıl: 2019 Cilt: 22 Sayı: 5 Sayfa Aralığı: 232 - 239 Metin Dili: İngilizce DOI: 10.14744/AnatolJCardiol.2019.83710 İndeks Tarihi: 13-06-2020

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

Öz:

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 combineduse 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. (Anatol J Cardiol 2019; 22: 232-9)

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1. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014; 740: 364-78.
2. El-Awady el-SE, Moustafa YM, Abo-Elmatty DM, Radwan A. Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies. Eur J Pharmacol 2011; 650: 335-41.
3. Patane S. Cardiotoxicity: cisplatin and long-term cancer survivors. Int J Cardiol 2014; 175: 201-2.
4. Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer 2013; 49: 2900-9.
5. Dugbartey GJ, Peppone LJ, de Graaf IA. An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures. Toxicology 2016; 371: 58-66.
6. Topal I, Ozbek Bilgin A, Keskin Cimen F, Kurt N, Suleyman Z, Bilgin Y, et al. The effect of rutin on cisplatin-induced oxidative cardiac damage in rats. Anatol J Cardiol 2018; 20: 136-42.
7. Bahadır A, Ceyhan A, Öz Gergin Ö, Yalçın B, Ülger M, Özyazgan TM, et al. Protective effects of curcumin and beta-carotene on cisplatin-induced cardiotoxicity: An experimental rat model. Anatol J Cardiol 2018; 19: 213-21.
8. Qian P, Yan LJ, Li YQ, Yang HT, Duan HY, Wu JT, et al. Cyanidin ameliorates cisplatin-induced cardiotoxicity via inhibition of ROS-mediated apoptosis. Exp Ther Med 2018; 15: 1959-65.
9. Ozben T. Oxidative stress and apoptosis: impact on cancer therapy. J Pharm Sci. 2007; 96: 2181-96.
10. Onay-Besikci A, Ozkan SA. Trimetazidine revisited: a comprehensive review of the pharmacological effects and analytical techniques for the determination of trimetazidine. Cardiovasc Ther 2008; 26: 147-65.
11. Molinari F, Pin F, Gorini S, Chiandotto S, Pontecorvo L, Penna F, et al. The mitochondrial metabolic reprogramming agent trimetazidine as an 'exercise mimetic' in cachectic C26-bearing mice. J Cachexia Sarcopenia Muscle 2017; 8: 954-73.
12. Chen PY, Hou CW, Shibu MA, Day CH, Pai P, Liu ZR, et al. Protective effect of Co-enzyme Q10 On doxorubicin-induced cardiomyopathy of rat hearts. Environ Toxicol 2017; 32: 679-89.
13. Fatima S, Al-Mohaimeed N, Al-Shaikh Y, Tyagi P, Banu N, Hasan S, et al. Combined treatment of epigallocatechin gallate and Coenzyme Q10 attenuates cisplatin-induced nephrotoxicity via suppression of oxidative/nitrosative stress, inflammation and cellular damage. Food Chem Toxicol 2016; 94: 213-20.
14. Scasso F, Sprio AE, Canobbio L, Scanarotti C, Manini G, Berta GN, et al. Dietary supplementation of coenzyme Q10 plus multivitamins to hamper the ROS mediated cisplatin ototoxicity in humans: A pilot study. Heliyon 2017; 3: e00251.
15. El-Sherbeeny NA, Attia GM. The protective effect of trimetazidine against cisplatin-induced nephrotoxicity in rats. Can J Physiol Pharmacol 2016; 94: 745-51.
16. Ateyya H, Yosef H, Nader MA. Ameliorative effect of trimetazidine on cisplatin-induced hepatotoxicity in rats. Can J Physiol Pharmacol 2016; 94: 225-30.
17. Astolfi L, Simoni E, Valente F, Ghiselli S, Hatzopoulos S, Chicca M, et al. Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats. PLoS One 2016; 11: e0162106.
18. Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, Kardeh B, Parsa Y, Salimi-Tabatabaee SA, et al. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat. Oxid Med Cell Longev 2016; 2016: 5818479.
19. Steggall A, Mordi IR, Lang CC. Targeting Metabolic Modulation and Mitochondrial Dysfunction in the Treatment of Heart Failure. Diseases 2017; 5: E14.
20. El-Agamy DS, El-Harbi KM, Khoshhal S, Ahmed N, Elkablawy MA, Shaaban AA, et al. Pristimerin protects against doxorubicin-induced cardiotoxicity and fibrosis through modulation of Nrf2 and MAPK/NFkB signaling pathways. Cancer Manag Res 2018; 11: 47-61.
21. Shinjo T, Tanaka T, Okuda H, Kawaguchi AT, Oh-Hashi K, Terada Y, et al. Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells. PLoS One 2018; 13: e0196191.
22. Hao E, Lang F, Chen Y, Zhang H, Cong X, Shen X, et al. Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor. PLoS One 2013; 8: e69452.
23. Li L, Du J, Lian Y, Zhang Y, Li X, Liu Y, et al. Protective Effects of Coenzyme Q10 Against Hydrogen Peroxide-Induced Oxidative Stress in PC12 Cell: The Role of Nrf2 and Antioxidant Enzymes. Cell Mol Neurobiol 2016; 36: 103-11.
24. Kabel AM, Elkhoely AA. Ameliorative Effect of Coenzyme Q10 and/ or Candesartan on Carboplatin-Induced Nephrotoxicity: Roles of Apoptosis, Transforming Growth Factor-Beta1, Nuclear Factor Kappa-B And The Nrf2/HO-1 Pathway. Asian Pac J Cancer Prev 2017; 18: 1629-36.
25. Liao XD, Wang XH, Jin HJ, Chen LY, Chen Q. Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts. Cell Res 2004; 14: 16-26.
26. Zhang P, Yi LH, Meng GY, Zhang HY, Sun HH, Cui LQ. Apelin-13 attenuates cisplatin-induced cardiotoxicity through inhibition of ROSmediated DNA damage and regulation of MAPKs and AKT pathways. Free Radic Res 2017; 51: 449-59.
27. Kisaoglu A, Borekci B, Yapca OE, Bilen H, Suleyman H. Tissue damage and oxidant/antioxidant balance. Eurasian J Med 2013; 45: 47-9.
28. Karthikeyan K, Bai BR, Devaraj SN. Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats. Int J Cardiol 2007; 115: 326-33.
29. Yüce A, Ateşşahin A, Ceribaşi AO, Aksakal M. Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharmacol Toxicol 2007; 101: 345-9.
30. Yousef MI, Saad AA, El-Shennawy LK. Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. Food Chem Toxicol 2009; 47: 1176-83.
31. Youn CK, Jo ER, Sim JH, Cho SI. Peanut sprout extract attenuates cisplatin-induced ototoxicity by induction of the Akt/Nrf2-mediated redox pathway. Int J Pediatr Otorhinolaryngol 2017; 92: 61-6.
32. Wang SW, Xu Y, Weng YY, Fan XY, Bai YF, Zheng XY, et al. Astilbin ameliorates cisplatin-induced nephrotoxicity through reducing oxidative stress and inflammation. Food Chem Toxicol 2018; 114: 227-36.
33. Zhang H, Liu M, Zhang Y, Li X. Trimetazidine Attenuates Exhaustive Exercise-Induced Myocardial Injury in Rats via Regulation of the Nrf2/NF-κB Signaling Pathway. Front Pharmacol 2019; 10: 175.
34. Eleftheriadis T, Pissas G, Liakopoulos V, Stefanidis I. Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage. Front Immunol 2016; 7: 279.
35. Kuzmicic J, Parra V, Verdejo HE, Lopez-Crisosto C, Chiong M, Garcia L, et al. Trimetazidine prevents palmitate-induced mitochondrial fission and dysfunction in cultured cardiomyocytes. Biochem Pharmacol 2014; 91: 323-36.
36. Kido K, Ito H, Yamamoto Y, Makita K, Uchida T. Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes. J Anesth 2018; 32: 120-31.

APA	ZHAO L (2019). Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. , 232 - 239. 10.14744/AnatolJCardiol.2019.83710
Chicago	ZHAO Li Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. (2019): 232 - 239. 10.14744/AnatolJCardiol.2019.83710
MLA	ZHAO Li Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. , 2019, ss.232 - 239. 10.14744/AnatolJCardiol.2019.83710
AMA	ZHAO L Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. . 2019; 232 - 239. 10.14744/AnatolJCardiol.2019.83710
Vancouver	ZHAO L Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. . 2019; 232 - 239. 10.14744/AnatolJCardiol.2019.83710
IEEE	ZHAO L "Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction." , ss.232 - 239, 2019. 10.14744/AnatolJCardiol.2019.83710
ISNAD	ZHAO, Li. "Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction". (2019), 232-239. https://doi.org/10.14744/AnatolJCardiol.2019.83710

APA	ZHAO L (2019). Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. The Anatolian Journal of Cardiology, 22(5), 232 - 239. 10.14744/AnatolJCardiol.2019.83710
Chicago	ZHAO Li Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. The Anatolian Journal of Cardiology 22, no.5 (2019): 232 - 239. 10.14744/AnatolJCardiol.2019.83710
MLA	ZHAO Li Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. The Anatolian Journal of Cardiology, vol.22, no.5, 2019, ss.232 - 239. 10.14744/AnatolJCardiol.2019.83710
AMA	ZHAO L Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. The Anatolian Journal of Cardiology. 2019; 22(5): 232 - 239. 10.14744/AnatolJCardiol.2019.83710
Vancouver	ZHAO L Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. The Anatolian Journal of Cardiology. 2019; 22(5): 232 - 239. 10.14744/AnatolJCardiol.2019.83710
IEEE	ZHAO L "Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction." The Anatolian Journal of Cardiology, 22, ss.232 - 239, 2019. 10.14744/AnatolJCardiol.2019.83710
ISNAD	ZHAO, Li. "Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction". The Anatolian Journal of Cardiology 22/5 (2019), 232-239. https://doi.org/10.14744/AnatolJCardiol.2019.83710