http://informahealthcare.com/txm ISSN: 1537-6516 (print), 1537-6524 (electronic) Toxicol Mech Methods, Early Online: 1–9 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/15376516.2015.1053648 RESEARCH ARTICLE Preventive effects of oleuropein against cardiac remodeling after myocardial infarction in Wistar rat through inhibiting angiotensin-converting enzyme activity Kais Mnafgui 1,2 , Ines Khlif 3 *, Raouf Hajji 2 *, Fatma Derbali 2 , Ftouma Kraiem 4 , Hedi Ellefi 5 , Thomas Michel 6,7 , Maria Halabalaki 7 , Alexios Leandros Skaltsounis 7 , Abdelfattah Elfeki 1 , Neji Gharsallah 8 , and Noureddine Allouche 3 1 Faculty of Sciences of Sfax, Laboratory of Animal Physiology, University of Sfax, Sfax, Tunisia, 2 Department of Internal Medicine, Hospital of Sidi Bouzid, Sidi Bouzid, Tunisia, 3 Faculty of Sciences of Sfax, Laboratory of Plant Biotechnology, Sfax, Tunisia, 4 Faculty of Medicine of Monastir, Monastir, Tunisia, 5 Department of Cardiology, Centre Hospitalier Intercommunal Robert Ballanger, Aulnay-Sous-Bois, France, 6 ICN, Universite ´ Nice Sophia Antipolis, Cedex, France, 7 Laboratory of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Athens, Greece, and 8 Faculty of Sciences of Sfax, Laboratory of Chemistry of Natural Products, Sfax, Tunisia Abstract Objective: Myocardial infarction remains the major cause of global death due to cardiovascular diseases. This study aimed to assess the protective role of oleuropein in attenuating the cardiac remodeling in isoproterenol-induced myocardial infarction in rats. Methods and results: Male Wistar rats were randomly divided into four groups, control, isoproterenol (Isop) and pretreated animals with oleuropein at two different doses (20 and 40 mg/kg) orally for 7 days and intoxicated with isoproterenol (Isop+Oleu20) and (Isop+Oleu40) groups. The subcutaneous injection of isoproterenol (100 mg/kg body weight) to untreated rats for two consecutive days showed significant increases in ST-segment elevation, heart weight index and alteration in the ECG pattern and hemodynamic function. Else, serum levels of cardiac troponin-T, creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) underwent a notable rise in serum of Isop group by (345, 82, 73 and 106%, respectively) as compared to normal rats. Isoproterenol-induced myocardial injury was evidenced by alteration in serum lipids profile and increased activities of pancreatic lipase by 94% and angiotensin-converting enzyme (ACE) by 78% which reflects the occurrence of cardiac remodeling process. The histopathological findings of the infarcted group showed myocardium necrosis and cells inflammatory infiltration. However, the treatment with oleuropein gave a good protection of the myocardium by decreasing cardiac injury markers specially troponin-T, restoring hemodynamic parameters and attenuating cardiac remodeling process through inhibition of ACE activity. Conclusion: Oleuropein offers high preventive effects from cardiac remodeling process in rats with acute myocardial infarction. Keywords ACE, cardiac remodeling, ECG, oleuropein, troponin-T History Received 8 March 2015 Revised 6 May 2015 Accepted 10 May 2015 Published online 9 June 2015 Introduction Acute myocardial infarction (AMI) and its resultant heart failure remains a major cause of morbidity and mortality worldwide by the coronary heart disease itself and its complication (Lozano et al., 2012). Myocardium necrosis marked the imbalance between coronary blood supply and cardiomyocytes needs, the heart and especially left ventricle responds by remodeling processes (Cohn et al., 2000). As a result, there are important histological changes including extracellular matrix deposition fibrosis and cardiomyocyte hypertrophy. Cardiac remodeling proceeding is expressed initially by hemodynamic modifications as an increase of systolic and diastolic left ventricular, internal diameter decrease of ejection fraction and fractional shortening, left ventricular structural and functional abnormalities; and later by clinical symptoms of heart failure (Mercanoglu et al., 2010; Salloum et al., 2008). Animal models are used to assess new approaches for the prevention and management of human AMI. In this respect, the administration of iso- proterenol to animal models in supramaximal dose induced infarct-like necrosis of the heart muscle, which morphologic- ally resembles AMI in humans (Kannan & Quine, 2011). Generally, the patients with AMI are treated by revascular- ization with thrombolytic agents or interventional procedures. *These two authors contributed equally to this work. Address for correspondence: Dr Kais Mnafgui, Faculty of Sciences of Sfax, Laboratory of Animal Physiology, University of Sfax, Sfax, Tunisia. Tel: +216 97 639 211. Fax: +216 74 274 437. E-mail: mnafgui_kais@yahoo.fr Toxicology Mechanisms and Methods Downloaded from informahealthcare.com by 197.5.2.100 on 06/09/15 For personal use only.