Bioimpacts. 2015;5(1):3-8. doi: 10.15171/bi.2015.02. Epub 2015 Feb 21.
Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat.
BioImpacts : BI
Hamid Soraya, Maryam Rameshrad, Aram Mokarizadeh, Alireza Garjani
Affiliations
Affiliations
- Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
- Cellular and Molecular Research Center, and Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
PMID: 25901291
PMCID: PMC4401166 DOI: 10.15171/bi.2015.02
Abstract
INTRODUCTION: 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).
CONCLUSION: 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.
Keywords: Cardiac remodeling; Metformin; Myocardial infarction; Neutrophil
References
- Cardiovasc Res. 1994 Sep;28(9):1414-22 - PubMed
- J Pharmacol Methods. 1985 Nov;14(3):157-67 - PubMed
- J Cardiovasc Pharmacol. 1991 Oct;18(4):581-8 - PubMed
- Circulation. 1989 Dec;80(6):1816-27 - PubMed
- J Am Coll Cardiol. 2003 Oct 15;42(8):1446-53 - PubMed
- Pharmacol Rep. 2012;64(6):1476-84 - PubMed
- Lancet. 1998 Sep 12;352(9131):854-65 - PubMed
- Am J Cardiol. 2004 Jun 1;93(11):1347-50, A5 - PubMed
- Heart Fail Rev. 2011 Jan;16(1):23-34 - PubMed
- Cardiovasc Drugs Ther. 2013 Feb;27(1):5-16 - PubMed
- Cardiovasc Res. 1999 Sep;43(4):860-78 - PubMed
- Circ Res. 2008 Feb 1;102(2):257-64 - PubMed
- Thromb Haemost. 2009 Aug;102(2):240-7 - PubMed
- J Biol Chem. 2004 Jul 30;279(31):32771-9 - PubMed
- Int Immunopharmacol. 2012 Dec;14(4):785-91 - PubMed
- Cardiovasc Ther. 2013 Feb;31(1):60-4 - PubMed
- Cardiovasc Res. 2004 Feb 15;61(3):481-97 - PubMed
- Circulation. 1983 May;67(5):1016-23 - PubMed
- Am J Physiol Lung Cell Mol Physiol. 2008 Sep;295(3):L497-504 - PubMed
- Metabolism. 2004 Feb;53(2):159-64 - PubMed
- Circ Res. 1989 Sep;65(3):657-70 - PubMed
- Circulation. 2002 Dec 10;106(24):3126-32 - PubMed
- J Clin Invest. 1973 Mar;52(3):599-607 - PubMed
- Cardiovasc Res. 2002 Jan;53(1):31-47 - PubMed
- Circ Res. 2004 Jun 25;94(12):1543-53 - PubMed
- Am Heart J. 2004 Feb;147(2):246-52 - PubMed
- Korean J Physiol Pharmacol. 2010 Dec;14(6):377-84 - PubMed
- Diabetes. 2008 Mar;57(3):696-705 - PubMed
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