Evaluate The Effect of Coenzyme Q10 on The Prevention of Doxorubicin-Induced Acute Cardiotoxicity in Rats.

Authors

  • Ola Sadeq AL-Shimaysawee Kufa Technical Institute, Al-Furat Al-Awsat Technical University, Najaf, Iraq; Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq
  • Fadhil A. Rizij Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq
  • Rafid Mohammed Ali Hassan wasfi Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq

DOI:

https://doi.org/10.22317/jcms.v10i1.1483

Keywords:

Keywords: Cardiotoxicity, Inflammatory markers, Oxidative- stress, Apoptosis, Coenzyme Q10, Doxorubicin.

Abstract

Objective: This study will evaluate the potential protective effects of coenzyme Q10 on DOX-induced cardiotoxicity in female rats, manifested by changes in biochemical parameters in tissue and serum samples histopathological differences, and compare their changes.

Methods:24 female rats were divided into three groups based on weight. The first group received saline, the second group received a cumulative dose of 15 mg/kg of DOX via IP injection, and the third group was pre-treated with CoQ10 before receiving DOX. The data were analysed using a one-way ANOVA test with a Bonferroni post hoc test to compare the markers and histopathological changes in different groups. The GraphPad Prism version 8.1 was used to do the statistical analysis.

Results: As indicated by a statistically significant increase (P<0.0001) in TNFα and ICAM-1 level, doxorubicin-induced cardiotoxicity. Additionally, the level of GSH, SOD, and caspase-3 did not differ significantly between the DOX+CoQ10 group and the control group. Furthermore, lesions and histological alterations were induced by the substance. Significant reductions in cardiotoxicity were observed with the administration of coenzyme Q10, as indicated by notable increases (P<0.0001) in SOD, GSH, and TNFα and significant decreases (P<0.0001) in caspase 3 when compared to the DOX group. Also, the CMYO score and lesions exhibited a substantial improvement.

Conclusion: In this investigation, coenzyme Q10 exhibited cardioprotective effects against DOX-induced damage to the mouse heart. This phenomenon potentially pertains to inhibiting and safeguarding against oxidative stress, the pathway of apoptosis, and the inflammatory response.

References

Yeh ETH, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy. Circulation. 2004;109(25):3122–31.

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer. 2013;49(6):1374–403.

Pizzino F, Vizzari G, Bomzer CA, Qamar R, Carerj S, Zito C, Khandheria BK. Diagnosis of chemotherapy-induced cardiotoxicity. J Patient Cent Res. Rev.; 2014; 1:121-27.

Raj, S., Franco, V. I., & Lipshultz, S. E. Anthracycline-induced cardiotoxicity: A review of pathophysiology, diagnosis, and treatment. Current Treatment Options in Cardiovascular Medicine. 2014; 16(6). 315-414.

Van der Zanden, S. Y., Qiao, X., & Neefjes, J. New insights into the activities and toxicities of the old anticancer drug doxorubicin. In FEBS Journal. 2021; (Vol. 288, Issue 21). 15-583.

Brana, L., & Tabernero, J. Cardiotoxicity. Annals of Oncology. 2010; 21(SUPPL. 7), 173-179.

Zhou H, Wang S, Zhu P, Hu S, Chen Y, Ren J. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol. 2018; 15: 335-346.

Sano M. A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J Cardiol. 2018;71: 471-476.

Yang S., Henikoff F., Teves, and Kemp. ‘Doxorubicin, DNA torsion, and chromatin dynamics.’ Biochimica et Biophysica Acta - Reviews on Cancer. The Authors. 2014; 1845(1), pp. 84–89.

Minotti, G., Menna, P., Salvatorelli, E., Cairo, G. and Gianni, L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004; 56(2), pp.185 -229.

Zhu, H., Sarkar, S., Scott, L., Danelisen, L., Trush, M.A., Jia, Z. and Li, R.Y. Doxorubicin Redox Biology: Redox Cycling, Topoisomerase Inhibition, and Oxidative Stress. Reactive Oxygen Species, 2016; 1(3), 189-198.

Abboud SH, Hadi NR, Assad HC, et al. Cardioprotective effects of erythropoietin against doxorubicin-induced cardiotoxicity in rats. World Heart J 2017; 9(3): 221–230.

KN, A. K., NS, B., MC, S., & KC, S. (2020). Degree-based topological indices on asthma drugs with QSPR analysis during covid-19. European Journal of Molecular & Clinical Medicine, 7(10), 53–66.

Sheibani, M., Azizi, Y., Shayan, M. et al. Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches. Cardiovasc Toxicol. 2022; 22, 292–310.

Wang XY, Yang CT, Zheng DD, et al. (2012) Hydrogen sulfide protects H9c2 cells against doxorubicin-induced cardiotoxicity through inhibition of endoplasmic reticulum stress. Mol Cell Biochem, 363(1–2):419–426.

Laredj, L.N., Licitra, F., Puccio, H.M. The molecular genetics of coenzyme Q biosynthesis in health and disease. Biochimie. 2014; 100, 78- 87.

Holmberg, M. J., Uber, A., Stankovic, N., Chen, C. O., Grossestreuer, A. V., Donnino, M. W., et al. Ubiquinol (reduced coenzyme Q10) and cellular oxygen consumption in patients undergoing coronary artery bypass grafting. Journal of Intensive Care Medicine. 2018; 1, 885066618789114.

Fouad, A. A., & Jresat, I. Hepatoprotective effect of coenzyme Q10 in rats with acetaminophen toxicity. Environmental Toxicology and Pharmacology. 2012; 33, 158–167.

Zhai, J., Bo, Y., Lu, Y., Liu, C., & Zhang, L. Effects of coenzyme Q10 on markers of inflammation: A systematic review and meta-analysis. PLoS ONE. 2017; 12, e0170172.

Jafari, M., Mousavi, S. M., Asgharzadeh, A., & Yazdani, N. Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews. Indian Heart Journal. 2018;7–0, 111–117.

Kawamukai M. Biosynthesis of coenzyme Q in eukaryotes. Biosci Biotechnol Biochem. 2016; 80:23–33.

Tran U, Clarke C. Endogenous synthesis of coenzyme Q in eukaryotes. Mitochondrion. 2007;7: S62–71.

Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension, and Meniere-like syndrome. Pharmacol Ther. 2009; 124:259–68.

Bentinger M, Tekle M, Dallner G. "Coenzyme Q--biosynthesis and functions." Biochemical and Biophysical Research Communications. 2010;396 (1): 74–9.

Hathcock JN, Shao A. "Risk assessment for coenzyme Q10 (Ubiquinone)". Regulatory Toxicology and Pharmacology. 2006;45 (3): 282–8.

Abdelkareem Aljumaily, S. A., Demir, M., Elbe, H et al. Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats. Environmental Science and Pollution Research. 2021; 28(46), 65802-65813.

Hekmat, A. S., Navabi, Z, Alipanah, H. et al. Alamandine significantly reduces doxorubicin-induced cardiotoxicity in rats. Human and Experimental Toxicology. 2021; 40(10), 1781-1795.

Botelho, A. F. M., Lempek, M. R., Branco, S. E. M., Nogueira, M. M., de Almeida, M. E., Costa, A. G., ... & Melo, M. M. Coenzyme Q10 cardioprotective effects against doxorubicin-induced cardiotoxicity in Wistar Rat. Cardiovascular Toxicology. 2020; 20(3), 222-234.

Xue, R., Wang, J., Yang, L., Liu, X., Gao, Y., Pang, Y., Wang, Y., & Hao, J. Coenzyme Q10 Ameliorates Pancreatic Fibrosis via the ROs-triggered mTOR Signaling Pathway. Oxidative medicine and cellular longevity, 2019;8039694.

Oliveira, M. S., Melo, M. B., Carvalho, J. L., Melo, I. M., Lavor, M. S., Gomes, D. A., de Goes, A. M., & Melo, M. M. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography. Journal of cancer science & therapy. 2013;5(2), 52–57.

Albakaa, R. N., Rizij, F. A., & Hassan, R. M. A. Potential Role of Empagliflozin to Ameliorate Doxorubicin Induced Cardiotoxicity in Male Rats, 2023.

Mobaraki, M., Faraji, A., Zare, M., Dolati, P., Ataei, M., & Manshadi, H. D. Molecular mechanisms of cardiotoxicity: a review on a major side-effect of doxorubicin. Indian J. Pharm. Sci. 2017; 79, 335-344.‏

Yu J.L.; Jin, Y.; Cao, X.Y.; Gu, H.H. Dexmedetomidine Alleviates Doxorubicin Cardiotoxicity by Inhibiting Mitochondrial Reactive Oxygen Species Generation. Hum. Cell. 2020; 33, 47–56.

Chen, P. Y., Hou, C. W., Shibu, M. A., Day, C. H., Pai, P., Liu, Z. R., ... & Huang, C. Y. Protective effect of Co‐enzyme Q10 On doxorubicin‐induced cardiomyopathy of rat hearts. Environmental toxicology. 2017; 32(2), 679-689.

Shabaan, D. A., Mostafa, N., El-Desoky, M. M., & Arafat, E. A. Coenzyme Q10 protects against doxorubicin-induced cardiomyopathy via antioxidant and anti-apoptotic pathways. Tissue Barriers. 2023; 11(1), 2019504.

Zhao L. Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction. Anatolian journal of cardiology. 2019; 22(5), 232–239.

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.

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.

Aryal B, and Rao VA. Deficiency in cardiolipin reduces doxorubicin-induced oxidative stress and mitochondrial damage in human B-lymphocytes. PLoS ONE. 2016;11(7): e0158376.

Byrne, N. J., Rajasekaran, N. S., Abel, E. D., & Bugger, H. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy. Free Radical Biology and Medicine. 2021; 169(March), 317–342.

Cecerska-Heryć, E., Surowska, O., Heryć, R., Serwin et al. Are antioxidant enzymes essential markers in the diagnosis and monitoring of cancer patients – A review? Clinical Biochemistry. 2021;93(March), 1–8.

Mustafa, H. N., Hegazy, G. A., El Awdan, S. A., & Abdelbaset, M. Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin-induced toxicity. Tissue and Cell. 2017; 49(3), 410-426.

Conklin, K. A. Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integrative Cancer Therapies. 2005; 4(2), 110-130.

Sun, Z., Yan, B., Yu, W.Y., Yao, X., Ma, X., Sheng, G., Ma, Q. Vitexin attenuates acute doxorubicin cardiotoxicity in rats via the suppression of oxidative stress, inflammation, and apoptosis and the activation of FOXO3a. Exp Ther Med. 2016; 12, 1879-1884.

Elsherbiny, N.M., Salama, M.F., Said, E., El-Sherbiny, M., Al-Gayyar, M.M. Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptotic pathways. Chem Biol Interact. 2016; 247, 39-48.

Tsuneki, H., Tokai, E., Suzuki, T., Seki, T., Okubo, K., Wada, T., ... & Sasaoka, T. Protective effects of coenzyme Q10 against angiotensin II-induced oxidative stress in human umbilical vein endothelial cells. European journal of pharmacology. 2013; 701(1-3), 218-227.

Xie, T., Wang, C., Jin, Y., Meng, Q., Liu, Q., Wu, J., & Sun, H. CoenzymeQ10-induced activation of AMPK-YAP-OPA1 pathway alleviates atherosclerosis by improving mitochondrial function, inhibiting oxidative stress, and promoting energy metabolism. Frontiers in pharmacology. 2020; 11, 1034.‏

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Published

2024-02-26

How to Cite

AL-Shimaysawee, O. S., Fadhil Abd aljabbar Rizij, & Rafid Mohammed Ali Hassan wasfi. (2024). Evaluate The Effect of Coenzyme Q10 on The Prevention of Doxorubicin-Induced Acute Cardiotoxicity in Rats. Journal of Contemporary Medical Sciences, 10(1). https://doi.org/10.22317/jcms.v10i1.1483