Toxicology 232 (2007) 216–225 Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study M. Rajadurai, P. Stanely Mainzen Prince Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608002, Tamil Nadu, India Received 20 November 2006; received in revised form 23 December 2006; accepted 7 January 2007 Available online 14 January 2007 Abstract This study was aimed to evaluate the preventive role of naringin on heart weight, blood glucose, total proteins, albumin/globulin (A/G) ratio, serum uric acid, serum iron, plasma iron binding capacity and membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na + /K + ATPase), calcium-dependent adenosine triphosphatase (Ca 2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg 2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats and in vitro free radical scavenging assay. Male albino Wistar rats were pretreated with naringin (10, 20 and 40 mg/kg, respectively) for a period of 56 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days. ISO-induced rats showed a significant (P < 0.05) increase in the heart weight, blood glucose, serum uric acid, serum iron and a significant (P < 0.05) decrease in the levels of total proteins, A/G ratio and iron binding capacity. A significant (P < 0.05) decrease in the activity of Na + /K + ATPase and increase in the activities of Ca 2+ and Mg 2+ ATPase in the heart and a significant (P < 0.05) increase in the levels of glycoproteins in serum and the heart were also observed in ISO-induced rats. Pretreatment with naringin for a period of 56 days exhibited a significant (P < 0.05) effect and altered these biochemical parameters positively in ISO-induced rats. Naringin also scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2 -azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and nitric oxide (NO) radicals in vitro. Thus, our study shows that naringin has cardioprotective role in ISO-induced MI in rats. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Naringin; Isoproterenol; Myocardial infarction; Glycoproteins; Membrane bound enzymes 1. Introduction Cardiovascular disease (CVD) remains the princi- pal cause of death in both developed and developing countries, accounting for roughly 20% of all deaths worldwide per year. Myocardial infarction (MI) is the rapid development of myocardial necrosis caused by Corresponding author. Tel.: +91 4144 238343; fax: +91 4144 238343. E-mail address: ps mainzenprince@yahoo.co.in (P. Stanely Mainzen Prince). critical imbalance between the oxygen supply and the demand of the myocardium. Oxidative stress resulting from increased production of free radicals associated with decreased levels of antioxidants in the myocardium, plays a major role in CVD such as ischemic heart disease, atherosclerosis, congestive heart failure, cardiomyopa- thy and arrhythmias (Das and Maulik, 1995). Damage to the myocardial cells arises due to the generation of toxic reactive oxygen species (ROS) such as superoxide radical, hydrogen peroxide and hydroxyl radical (Vaage and Valen, 1993). Free radical production is an enzyme catalyzed as well as electron transfer process, which is an important phenomenon in the cell metabolism. 0300-483X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2007.01.006