Toxicology 228 (2006) 259–268 Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: Biochemical and histopathological evidences M. Rajadurai, P. Stanely Mainzen Prince ∗ Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India Received 28 July 2006; received in revised form 15 September 2006; accepted 18 September 2006 Available online 24 September 2006 Abstract This study was designed to evaluate the cardioprotective potential of naringin on lipid peroxides, enzymatic and nonenzymatic antioxidants and histopathological findings in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg) to male Wistar rats showed a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and the heart and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the heart and the levels of reduced glutathione, vitamin C and vitamin E in plasma and heart and ceruloplasmin in plasma. Oral administration of naringin (10, 20 and 40 mg/kg, respectively) to ISO-induced rats daily for a period of 56 days showed a significant decrease in the levels of lipid peroxidative products and improved the antioxidant status by increasing the activities of antioxidant enzymes and nonenzymatic antioxidants. Histopathological findings of the myocardial tissue showed the protective role of naringin in ISO-induced rats. The effect at a dose of 40 mg/kg of naringin was more pronounced than that of the other two doses, 10 and 20 mg/kg. The results of our study show that naringin possess anti-lipoperoxidative and antioxidant activity in experimentally induced cardiac toxicity. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Naringin; Isoproterenol; Myocardial infarction; Lipid peroxidation; Antioxidants 1. Introduction Ischemic heart disease (IHD) is the leading cause of morbidity and mortality in the Western world, and according to the World Health Organization, it will be the major cause of death in the world by the year 2020 (Lopez and Murrau, 1998). IHD is a condition in which an imbalance between myocardial oxygen supply and ∗ Corresponding author. Tel.: +91 4144 238343; fax: +91 4144 239141. E-mail address: ps mainzenprince@yahoo.co.in (P. Stanely Mainzen Prince). demand results in myocardial hypoxia and accumulation of waste metabolites most often due to atherosclerotic disease of the coronary arteries (Hegstad et al., 1994). It is well known that ischemic tissue generates oxygen- derived free radicals, and often leading to chain reactions which contribute to cell death (Cai et al., 1997). Isoproterenol (ISO), a synthetic catecholamine and a -adrenergic agonist causes severe oxidative stress in the myocardium, resulting in infarct like necrosis of the heart muscles (Wexler, 1978). Catecholamines rapidly undergo autooxidation and has been suggested that the oxidative products of catecholamines are responsible for the changes in the myocardium (Yates and Dhala, 0300-483X/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2006.09.005