Cardioprotective action of metformin in experimental isoproterenol-induced myocardial infarction

D.Ch. Aningo; O.O. Levenets; D.B. Koval; K.L. Ostroverha; Halyna Ya. Loi; Mykola P. Klanza; Valentyna V. Chernyashova; Oleksandra M.  Oleshchuk

Summary. Myocardial infarction (MI) occurs more frequently in patients with diabetes mellitus (DM) than in the general population and is characterized by a less favorable prognosis. Metformin is a first-line drug for the treatment of type 2 diabetes, which is known for its pronounced cardioprotective effect. The aim of the study – to investigate the antihypertrophic and antiapoptotic effects of metformin and its effect on the expression of brain natriuretic peptide (BNP) in isoproterenol (Iso) induced MI. Materials and Methods. The study was performed on 50 white adult male rats. MI was induced by 2 injections of Iso (100 mg/kg) with 24 hours interval. Treatment with metformin (200 mg/kg) was performed for 7 days from the first day of the experiment. Histological sections of the myocardium were stained with hematoxylin and eosin. BNP expression was examined using the Rat BNP ELISA Kit (Elabscience). Statistical comparison of multiple groups was performed by one-way ANOVA followed by a Bonferroni post hoc test. Results. Rats receiving Iso injections had a twofold increase in cardiomyocyte areas from (230.30±3.64) μm2 in (C) group to (490.6±8.93) μm2 in (Iso) group. Metformin treatment prevented hypertrophic changes in cardiomyocytes in MI, as their area remained 58 % smaller. In rats with MI, serum BNP concentrations increased by 77 %: (191.90±8.20) pg/ml in group (Iso) vs (108.0±8.36) pg/ml in control group (C). Metformin treatment reduced BNP concentrations by 29 % to (136.10±2.76) pg/ml in rats with MI. Iso administration resulted in massive accumulation of fibrotic tissue from (0.19±0.01) % in (C) group to (32.08±2.46) % in (Iso) group. Metformin inhibited fibrotic changes in rats with MI by almost 10-fold. Conclusions. In isoproterenol-induced MI in rats, metformin prevents cardiac hypertrophy, inhibits the expression of the prohypertrophic marker BNP and suppresses fibrotic remodeling

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