Effect of Metformin Pretreatment on Serum Adropin Level in Rats with Adrenalin-Induced Acute Myocardial Infarction

Abstract
Background: Beside adropin's role in energy homeostasis and insulin sensitivity, it is also incriminated in myocardial ischemia. Level of adropin during myocardial infarction (MI) and the effect of metformin pretreatment on serum adropin level in rat models of MI is underinvestigated.
Aim of Study: This study investigated the level of adropin in MI and the possible involvement of adropin and endothelial nitric oxide synthase enzyme activity (eNOS) in the cardio-protective effect of metformin during acute myocardial ischemia.
Material and Methods: A total of forty adult male albino rats weighing 185-220g were divided equally into four groups Group I: Normal control group. Group II: MI group, which was induced by subcutaneous injection of adrenalin (2mg/kg) in two doses 24 hours apart. Group III: Normal rats which were treated with oral metformin via a feeding tube in a dose of 300mg/kg for 2 weeks. Group IV: Rats with adrenalin-induced MI and pretreated with oral metformin in the same dose and duration before induction of MI on the 13th and 14th days of the study. Serum adropin and eNOS were measured, in addition to cardiac troponin I, Creatine Kinase isoenzyme (CK-MB), and C-reactive protein (CRP). Sections from the heart was stained with Masson's trichrome stain and examined to quantify the degree of ischemic injury at the tissue level.
Results: In MI group, both serum adropin level and the eNOS were significantly increased with significant positive correlation between adropin and troponin I, CK-MB, and eNOS in the same group (r= 0.857, 0.97 & 0.845, respectively, p<0.05). However, Metformin pretreatment in group IV, produced significant reduction in the level of adropin accom-panied by significant increase in levels of eNOS enzyme activity in comparison to rats with untreated MI. Additionally histological examination, showed reduction of the inflamma-tory cell infiltration, myocardial fibrosis and necrosis. More-over, there was a positive correlation between adropin and eNOS in the same group (r=0.682, p<0.05).
Conclusion: Adropin and eNOS enzyme play a vital role in the pathophysiology of acute myocardial infarction. In addition, the cardioprotective effect of metformin pretreatment in this condition depends on enhancing the activity of eNOS enzyme independent on adropin level.