Skip to main content
PMC home page
Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2009 Dec;70(6):460–471. doi: 10.1016/j.curtheres.2009.12.004

Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

Arvindkumar E Ghule 1, Chetan P Kulkarni 1, Subhash L Bodhankar 1,*, Vijaya A Pandit 2
PMCID: PMC3969979  PMID: 24692838

Abstract

Background: Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions.

Objective: The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats.

Methods: Albino male Wistar rats (250–300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9–18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician.

Results: A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly lower myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.01]); and significantly higher serum activities of marker enzymes (eg, CK-MB [P < 0.001] and LDH [P < 0.001]). Compared with the ISO group, the CoQ10 + ISO group had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly lower MDA concentration [P < 0.05]; significantly higher myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.05]); and significantly lower serum activities of marker enzymes (eg, CK-MB [P < 0.05] and LDH [P < 0.01]).

Conclusion: Pretreatment with CoQ10 (100 mg/kg) for 18 days was associated with moderate protection against ISO-induced cardiotoxicity and cardiac hypertrophy, and with lower myocardial injury by preserving endogenous antioxidants and reducing LPO in rat heart.

Key words: antioxidants, cardiac hypertrophy, coenzyme Q10, isoproterenol

Full Text

The Full Text of this article is available as a PDF (126.5 KB).

References

  • 1.Choudhary R, Mishra KP, Subramanyam C. Prevention of isoproterenol-induced cardiac hypertrophy by eugenol, an antioxidant. Ind J Clin Biochem. 2006;21:107–113. doi: 10.1007/BF02912923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ennis IL, Escudero EM, Console GM. Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition. Hypertension. 2003;41:1324–1329. doi: 10.1161/01.HYP.0000071180.12012.6E. [DOI] [PubMed] [Google Scholar]
  • 3.Prince PS, Rajadurai M. Preventive effect of Aegle marmelos leaf extract on isoprenalineinduced myocardial infarction in rats: Biochemical evidence. J Pharm Pharmacol. 2005;57:1353–1357. doi: 10.1211/jpp.57.10.0015. [DOI] [PubMed] [Google Scholar]
  • 4.Sathish V, Ebenezar KK, Devaki T. Synergistic effect of nicorandil and amlodipine on tissue defense system during experimental myocardial infarction in rats. Mol Cell Biochem. 2003;243:133–138. doi: 10.1023/a:1021612230000. [DOI] [PubMed] [Google Scholar]
  • 5.Battino M, Ferri E, Gorini A. Natural distribution and occurrence of coenzyme Q homologues. Membr Biochem. 1990;9:179–190. doi: 10.3109/09687689009025839. [DOI] [PubMed] [Google Scholar]
  • 6.Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta. 2004;1660:171–199. doi: 10.1016/j.bbamem.2003.11.012. [DOI] [PubMed] [Google Scholar]
  • 7.Ernster L, Dallner G. Biochemical physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995;1271:195–204. doi: 10.1016/0925-4439(95)00028-3. [DOI] [PubMed] [Google Scholar]
  • 8.Sunamori M, Tanaka H, Maruyama T. Clinical experience of coenzyme Q10 to enhance intraoperative myocardial protection in coronary artery revascularization. Cardiovasc Drugs Ther. 1991;5(Suppl 2):297–300. doi: 10.1007/BF00054751. [DOI] [PubMed] [Google Scholar]
  • 9.Kagan V, Serbinova E, Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun. 1990;169:851–857. doi: 10.1016/0006-291x(90)91971-t. [DOI] [PubMed] [Google Scholar]
  • 10.Das DK, Maulik N. Protection against free radical injury in the heart and cardiac performance. In: Sen CK, Packer L, Hänninen O, editors. Exercise and Oxygen Toxicity. Elsevier; New York, NY: 1994. pp. 359–388. [Google Scholar]
  • 11.Slater TF, Sawyer BC. The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro. General features of the systems used. Biochem J. 1971;123:805–814. doi: 10.1042/bj1230805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582:67–78. doi: 10.1016/0304-4165(79)90289-7. [DOI] [PubMed] [Google Scholar]
  • 13.Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247:3170–3175. [PubMed] [Google Scholar]
  • 14.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–275. [PubMed] [Google Scholar]
  • 15.Teerlink JR, Pfeffer J, Pfeffer MA. Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats. Circ Res. 1994;75:105–113. doi: 10.1161/01.res.75.1.105. [DOI] [PubMed] [Google Scholar]
  • 16.Hamilton GW, Murray JA, Kennedy JW. Quantitative angiocardiography in ischemic heart disease. The spectrum of abnormal left ventricular function and the role of abnormally contracting segments. Circulation. 1972;45:1065–1080. doi: 10.1161/01.cir.45.5.1065. [DOI] [PubMed] [Google Scholar]
  • 17.Kitamura S, Kay JH, Krohn BG. Geometric and functional abnormalities of the left ventricle with a chronic localized noncontractile area. Am J Cardiol. 1973;31:701–707. doi: 10.1016/0002-9149(73)90003-9. [DOI] [PubMed] [Google Scholar]
  • 18.Hori M, Inoue M, Mishima M. Infarct size and left ventricular ejection fraction in acute myocardial infarction. Japan Circ J. 1977;41:1299–1306. [PubMed] [Google Scholar]
  • 19.Gibson DG, Brown DJ. Continuous assessment of left ventricular shape in man. Br Heart J. 1975;37:904–910. doi: 10.1136/hrt.37.9.904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Tomlinson CW. Left ventricular geometry and function in experimental heart failure. Can J Cardiol. 1987;3:305–310. [PubMed] [Google Scholar]
  • 21.Wheatley AM, Thandroyen FT, Opie LH. Catecholamine-induced myocardial cell damage: Catecholamines or adrenochrome. J Mol Cell Cardiol. 1985;17:349–359. doi: 10.1016/s0022-2828(85)80134-6. [DOI] [PubMed] [Google Scholar]
  • 22.Brodde OE. Beta 1- and beta 2-adrenoceptors in the human heart: Properties, function, and alterations in chronic heart failure [published correction appears in Pharmacol Rev. 1991;43:350] Pharmacol Rev. 1991;43:203–242. [PubMed] [Google Scholar]
  • 23.Remião F, Carmo H, Carvalho F, Bastos ML. Copper enhances isoproterenol toxicity in isolated rat cardiomyocytes: Effects on oxidative stress. Cardiovasc Toxicol. 2001;1:195–204. doi: 10.1385/ct:1:3:195. [DOI] [PubMed] [Google Scholar]
  • 24.Dhalla KS, Rupp H, Beamish RE, Dhalla NS. Mechanisms of alterations in cardiac membrane Ca2+ transport due to excess catecholamines. Cardiovasc Drugs Ther. 1996;10(Suppl 1):231–238. doi: 10.1007/BF00120492. [DOI] [PubMed] [Google Scholar]
  • 25.Shimomura Y, Suzuki M, Sugiyama S. Protective effect of coenzyme Q10 on exercise-induced muscular injury. Biochem Biophys Res Commun. 1991;176:349–355. doi: 10.1016/0006-291x(91)90931-v. [DOI] [PubMed] [Google Scholar]
  • 26.Okamoto T, Kubota N, Takahata K. Protective effect of coenzyme Q10 on cultured skeletal muscle cell injury induced by continuous electric field stimulation. Biochem Biophys Res Commun. 1995;216:1006–1012. doi: 10.1006/bbrc.1995.2720. [DOI] [PubMed] [Google Scholar]
  • 27.Saravanan G, Prakash J. Effect of garlic (Allium sativum) on lipid peroxidation in experimental myocardial infarction in rats. J Ethnopharmacol. 2004;94:155–158. doi: 10.1016/j.jep.2004.04.029. [DOI] [PubMed] [Google Scholar]
  • 28.Zhou R, Xu Q, Zheng P. Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol. 2008;586:244–250. doi: 10.1016/j.ejphar.2008.02.057. [DOI] [PubMed] [Google Scholar]
  • 29.Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res. 1998;38:297–303. doi: 10.1006/phrs.1998.0365. [DOI] [PubMed] [Google Scholar]
  • 30.Srivastava S, Chandrasekar B, Gu Y. Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res. 2007;74:445–455. doi: 10.1016/j.cardiores.2007.02.016. [DOI] [PubMed] [Google Scholar]
  • 31.Hemnani T, Parihar MS. Reactive oxygen species and oxidative DNA damage. Indian J Physiol Pharmacol. 1998;42:440–452. [PubMed] [Google Scholar]
  • 32.Banerjee SK, Sood S, Dinda AK. Chronic oral administration of raw garlic protects against isoproterenol-induced myocardial necrosis in rat. Comp Biochem Physiol C Toxicol Pharmacol. 2003;136:377–386. doi: 10.1016/j.cca.2003.10.011. [DOI] [PubMed] [Google Scholar]

Articles from Current Therapeutic Research, Clinical and Experimental are provided here courtesy of Elsevier

RESOURCES