Egyptian Journal of Basic and Clinical Pharmacology Dec. 2012, Vol. 2., No. 2. 13-22 http://www.ejbcp.eg.net/ 35 Original Article Isoprenaline-induced myocardial infarction in rats: protective effects of hesperidin. Mai A. Zaafan 1 , Hala F. Zaki, Amany I. El-Brairy 1 , Sanaa A. Kenawy Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Egypt 1 Pharmacology & Toxicology Department, Faculty of Pharmacy, MSA University, Egypt. A B S T R A C T Myocardial infarction is amongst the most common causes of death worldwide. The present study aimed to investigate the cardioprotective effect of hesperidin (200 mg/kg) either individually or in combination with atorvastatin (10 mg/kg), as a reference standard, in isoprenaline-induced myocardial infarction in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), oxidative stress biomarkers including cardiac contents of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) as well as serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). Furthermore, ECG monitoring and histologic examinations of cardiac tissues were done. Isoprenaline increased CK-MB activity as the well the levels of cTn-I, inflammatory and oxidative stress biomarkers. In addition, it produced ST segment elevation and degenerative changes in heart tissues. The obtained data revealed that pretreatment with hesperidin alone or in combination with atorvastatin significantly decreased the elevated activity of serum CK- MB as well as serum levels of cTn-I, CRP, TNF-α and IL-10 coupled by a reduction in cardiac lipid peroxides and NO content. Moreover, both treatments resulted in marked improvement in isoprenaline-induced ECG and histopathologic changes. In conclusion, hesperidin can be regarded as a promising cardioprotective natural agent in myocardial infarction when used alone or combined with atorvastatin. Key Words: Hesperidin, isoprenaline, myocardial infarction, C-reactive protein, cytokines, oxidative stress. Corresponding Author: Hala F. Zaki, PhD. Email: halafzaki@gmail.com 1. INTRODUCTION Myocardial infarction (MI), the most dreaded sequel among coronary heart diseases, is the rapid development of myocardial necrosis because of total deprivation of blood supply to an area of cardiac muscle for an appreciable period of time (Vennila and Pugalendi, 2010). Inflammation is a key process involved in mediating myocardial tissue damage after an ischemic event (Tawfik et al., 2010). Neutrophils infiltrate to the infarcted area and can promote myocardial cell damage through the release of proteolytic enzymes and/or production of reactive oxygen species (ROS). Inflammation may also increase the risk of recurrent ischemic events by destabilizing atherosclerotic plaques and making them prone to rupture (Jordan et al., 1999). Isoprenaline, a β-adrenergic agonist, has been reported to produce MI in large doses (Padmanabhan et al., 2008). Upon auto-oxidation, isoprenaline generates highly cytotoxic free radicals known to stimulate peroxidation of membrane phospholipids causing severe damage to myocardial membrane. Hence, it is widely used as a model for induction of MI in rats (Panda and Naik, 2009). Hesperidin is a citrus bioflavonoid with wide biological and pharmacological properties including anti-carcinogenic, antioxidative, vascular protective and lipid-lowering activities (Morand et al., 2011; Wang et al., 2011). It is a potent anti-inflammatory agent with reported protection against in vivo focal myocardial ischemia/reperfusion injury-induced arrhythmias and apoptosis (Gandhi et al., 2009). Copyright © 2012 Mai A. Zaafan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly .cited