title: Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat.
abstract: BACKGROUND
  Acute treatment with metformin has a cardio-protective effects by suppression of inflammatory responses during myocardial infarction (MI) through activation of AMP-activated protein kinase (AMPK). Neutrophils have a pivotal role during MI-induced inflammatory responses. Some anti-inflammatory treatments have decreased cardiac injury and infarct size in MI. Here we evaluated the effects of chronic pre-treatment with metformin on myocardial remodeling and neutrophil recruitment after isoproterenol-induced MI.
  
  
  METHODS
  Male wistar rats were randomly assigned into 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 hearts. Number of neutrophils in peripheral blood and their infiltration to myocardium were evaluated by Gimsa staining 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 to body weight ratio was also decreased with all doses of metformin. Pre-treatment with metformin in comparison to Iso (MI) group reduced peripheral neutrophils (p<0.05, p<0.01, and p<0.001 at 25, 50, and 100 mg/kg; respectively) as well as MPO activity (p<0.05 and p<0.01 at 50 and 100 mg/ kg, respectively).
  
  
  CONCLUSIONS
  Pre-treatment with metformin decreased post-MI myocardial injuries by reducing cardiac remodeling and myocardial neutrophil activity. The results could be explained as a new mechanism for cardio-protective effect of metformin.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Soraya
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rameshrad
authors.affiliation: Cellular and Molecular Research Center, and Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
authors.forename: Aram
authors.initials: A
authors.lastname: Mokarizadeh
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Garjani
keywords: Cardiac remodeling; Metformin; Myocardial infarction; Neutrophil