Ellagic acid improved arrhythmias induced by CaCL2 in the rat stress model

Document Type : Original Research Article

Authors

Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective: In ventricular arrhythmias, due to their free radical scavenging action, antioxidant agents are usually used in the treatment of cardiovascular disease. Since stress is considered as risk factor for increased mortality by causing malignant arrhythmias, the study was designed to evaluate the cardioprotective effects of ellagic acid (EA) on CaCl2-induced arrhythmias in rat stress model.
Materials and Methods: Male Sprague-Dawley rats (200-250 g) were divided into four groups: Group I: Control rats (2 ml of saline by gavage), Group II: Rats treated with EA (15 mg/kg, gavage), Group III: stress group, Group IV: received EA plus stress. Stress was applied in a restrainer box (6 hour/day, 21 days). After induction of anesthesia, lead II electrocardiogram was recorded for calculating heart rate and QRS complex. The arrhythmia was produced by injection of CaCl2 solution (140 mg/kg, iv) and incidences of Ventricular fibrillation, Ventricular premature beats and Ventricular tachycardia were recorded. Results were analyzed by using one-way ANOVA and Fisher`s exact test. pResults: The results showed a positive inotropic effect and negative chronotropic effect for the EA group in comparison with the control group. Incidence rates (%) of premature beats, ventricular fibrillation and ventricular tachycardia in stress group and all the arrhythmia parameters decreased in groups which received EA.
Conclusions:  By decreasing the incidence rates of premature beats, fibrillation and ventricular tachycardia in groups which received EA, ellagic acid probably acted as an anti-arrhythmic agent which showed to have aprotective functionin heart.

Keywords

Main Subjects


Antipenko AY, Spielman AI, Kirchberger MA. 1999. Interactions of 6-gingerol and ellagic acid with the cardiac sarcoplasmic reticulum Ca2+-ATPase. J Pharmacol Exp Ther, 290: 227-234.
Belevych AE, Terentyev D, Viatchenko-Karpinski S, Terentyeva R, Sridhar A, Nishijima Y, Wilson LD, Cardounel AJ, Laurita KR, Carnes CA, Billman GE, Gyorke S. 2009. Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death. Cardiovasc Res, 84: 387-395.
Beresewicz A, Horackova M. 1991. Alterations in electrical and contractile behavior of isolated cardiomyocytes by hydrogen peroxide: possible ionic mechanisms. J Mol Cell Cardiol, 23: 899-918.
Carnevali  L, Mastorci F, Audero E, Graiani G, Rossi S, Macchi  E, Callegari S, Bartolomucci A, Nalivaiko E, Quaini F, Gross C, Sgoifo A. 2012. Stress-induced susceptibility to sudden cardiac death in mice with altered serotonin homeostasis. PLoS One, 7: e41184.
Chen K, Keaney JF Jr. 2012. Evolving concepts of oxidative stress and reactive oxygen species in cardiovascular disease. Curr Atheroscler Rep, 14: 476-483.
Chugh SS, Reinier  K, Teodorescu  C, Evanado  A, Kehr  E, Al Samara  M, Mariani  R, Gunson  K, Jui  J. 2008. Epidemiology of Sudden Cardiac Death: Clinical and Research Implications. Progress in Cardiovascular Diseases, 51: 213-228.
Daniel  EM, Krupnick  AS, Heur YH, Blinzler  JA, Nims RW, Stoner  GD. 1989. Extraction, stability, and quantitation of ellagic acid in various fruits and nuts. Journal of food composition and Analysis, 2: 338-349.
Devipriya  N, Srinivasan  M, Sudheer AR, Menon VP. 2007. Effect of ellagic acid, a natural polyphenol, on alcohol-induced prooxidant and antioxidant imbalance: a drug dose dependent study. Singapore Med J, 48: 311-318.
Dianat M, Akbari  GH, Badavi M. 2013. Antidysrhythmic Effects of Gallic acid on cacl2-induced arrhythmia in rat.Int J Res Dev Pharm L Sc, 2: 686-689.
Elfalleh W, Tlili N, Nasri N, Yahia Y, Hannachi H, Chaira N, Ying M, Ferchichi A. 2011. Antioxidant capacities of phenolic compounds and tocopherols from Tunisian pomegranate (Punica granatum) fruits. J Food Sci, 76: C707-713.
Furuuchi R, Sakai H, Hirokawa N, Watanabe  Y, Yokoyama  T, Hirayama  M. 2012. Antihypertensive effect of boysenberry seed polyphenols on spontaneously hypertensive rats and identification of orally absorbable proanthocyanidins with vasorelaxant activity. Biosci Biotechnol Biochem, 76: 1694-1701.
Gelvan D, Saltman P, Powell SR. 1991. Cardiac reperfusion damage prevented by a nitroxide free radical. Proc Natl Acad Sci U S A, 88: 4680-4684.
Grumbach L, Howard JW, Merrill VI. 1954. Factors related to the initiation of ventricular fibrillation in the isolated heart; effect of calcium and potassium. Circ Res, 2: 452-459.
He G, Hu J, Li T, Ma X, Meng J, Jia M, Lu J, Ohtsu H, Chen Z, Luo X. 2012. Arrhythmogenic effect of sympathetic histamine in mouse hearts subjected to acute ischemia. Mol Med, 18: 1-9.
He RR, Yao N, Wang M, Yang XS, Yau CC, Abe K, Yao XS, Kurihara H. 2009. Effects of histamine on lipid metabolic disorder in mice loaded with restraint stress. J Pharmacol Sci, 111: 117-123.
Irwin J, Ahluwali P, Anisman H. 1986. Sensitization of norepinephrine activity following acute and chronic footshock. Brain Res, 379: 98-103.
Kannan MM, Quine  SD. 2011. Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study. Eur J Pharmacol, 659 45–52.
Kannan  MM, Quine SD. 2013. Ellagic acid inhibits cardiac arrhythmias, hypertrophy and hyperlipidaemia during myocardial infarction in rats. Metabolism, 62: 52-61.
Karagueuzian HS, Nguyen TP, Qu Z, Weiss JN. 2013. Oxidative stress, fibrosis, and early afterdepolarization-mediated cardiac arrhythmias. Front Physiol, 4: 19.
Kaushik S, Kaur J. 2003. Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clin Chim Acta, 333: 69-77.
Khori V, Nayebpour M. 2007. Effect of artemisia absinthium on electrophysiological properties of isolated heart of rats. Physiology & Pharmacology Journal, 10: 303-311.
Kumaran KS, Prince PS. 2010. Protective effect of caffeic acid on cardiac markers and lipid peroxide metabolism in cardiotoxic rats: an in vivo and in vitro study. Metabolism, 59: 1172-1180.
Liu YB, Wu CC, Lee CM, Chen WJ, Wang TD, Chen PS, Lee YT. 2006. Dyslipidemia is associated with ventricular tachyarrhythmia in patients with acute ST-segment elevation myocardial infarction. J Formos Med Assoc, 105: 17-24.
Malinow MR, Batlle FF, Malamud B. 1953. Nervous mechanisms in ventricular arrhythmias induced by calcium chloride in rats. Circ Res, 1: 554-559.
Marin MT, Cruz FC, Planeta CS. 2007. Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats. Physiol Behav, 90: 29-35.
McLaughlin KJ, Gomez JL, Baran SE,Conrad CD. 2007. The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Brain Res, 1161: 56-64.
Meerson FZ. 1994. Stress-induced arrhythmic disease of the heart--Part I. Clin Cardiol, 17: 362-371.
Rozanski, A, Blumenthal, JA,Kaplan, J. 1999. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation, 99: 2192-2217.
Rubart  M, Zipes DP. 2005. Mechanisms of sudden cardiac death. J Clin Invest, 115: 2305-2315.
Tamargo J, Caballero R, Gomez R, Nunez L, Vaquero M, Delpon E. 2007. Lipid-lowering therapy with statins, a new approach to antiarrhythmic therapy. Pharmacol Ther, 114: 107-126.
Zhu M, Phillipson JD, Greengrass PM, Bowery NE, Cai Y. 1997. Plant polyphenols: biologically active compounds or non-selective binders to protein? Phytochemistry, 44: 441-447.