Aram Mokarizadeh, Hamid Soraya and Alireza Garjani
Department of Immunology, Kurdistan University of Medical Sciences, Sanandaj, Iran
Background: Acute treatment with metformin has a cardio-protective effect by suppression of inflammatory responses during myocardial infarction (MI). Neutrophils have a pivotal role during MI-induced inflammatory responses. Some anti-inflammatory treatments have decreased the cardiac injury and infarct size in MI. In this study we evaluated the effect of chronic pre-treatment with metformin on myocardial remodeling and neutrophil recruitment after isoproterenol-induced MI in rats.
Methods: Male wistar rats were randomly assigned to 6 groups (n=6) of untreated control, sham, isoproterenol (Iso), and pre-treated orally with 25, 50, and 100 mg/kg of metformin, twice daily, for 14 days. Isoproterenol was injected subcutaneously (sc) at 13th and 14th days for induction of acute MI. Histopathological examinations were done on the harvested heart. Number of neutrophils in peripheral blood and their infiltration to myocardium were evaluated by Gimsa coloring and myeloperoxidase (MPO) assay respectively.
Results: Histopathological analysis showed a significant attenuation of isoproterenol-induced cardiomyocyte necrosis and fibrosis by all three doses of metformin. The heart weight to body weight ratio also was decreased with all doses of metformin. Pre-treatment with metformin in comparsion to ISO (MI) group reduced peripheral neutrophils (p <0.05, p<0.01, and p<0.001 in 25, 50, and 100 mg/kg; respectively) as well as myeloperoxidase (MPO) activity (p<0.05 and p<0.01 in 50 and 100 mg/kg, respectively). Conclusions: Chronic pre-treatment with metformin decrease myocardial injuries after MI by reducing cardiac remodeling as well as peripheral and myocardial neutrophil activity. So this could be explained as a new mechanism for cardio-protective effect of metformin.
Keywords: Metformin, Neutrophil, Myocardial infarction.