Abstract
We substantiated the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in the protective effect of apigenin against the myocardial infarction (MI) in diabetic rats. Diabetes was induced by intraperitoneal administration of a single dose of streptozotocin (55 mg/kg). The study groups included diabetic rats receiving vehicle, apigenin (75 mg/kg/day, orally), GW9662 (1 mg/kg/day, intraperitoneally), and a combination of apigenin and GW9662 for 14 days. The MI was induced in all the study groups except the diabetic control group by subcutaneous injection of 100 mg/kg/day of isoproterenol on the two terminal days. The diabetes and isoproterenol-induced MI was evident as a reduction in the maximal positive and negative rate of developed left ventricular pressure and an increase in the left ventricular end-diastolic pressure. The activities of creatine kinase on myocardial bundle (CK-MB) and lactate dehydrogenase (LDH) were also reduced. Apigenin treatment prevented the hemodynamic perturbations, restored the left ventricular function and reinstated a balanced redox status. It protected rats against an MI by attenuating myonecrosis, edema, cell death, and oxidative stress. GW9662, a PPAR-γ antagonist reversed the myocardial protection conferred by apigenin. Further, an increase in the PPAR-γ expression in the myocardium of the rats receiving apigenin reinforces the role of PPAR-γ pathway activation in the cardioprotective effects of apigenin.
Highlights
Diabetes increases the mortality rate during an acute myocardial infarction (MI) and contributes to the higher morbidity in the post-infarction patients [1]
We investigated the effects of apigenin on isoproterenol-induced MI in diabetic rats
The diabetic myocardial infarcted rats treated with apigenin alone or in combination with GW9662 showed significant decreases in the blood glucose level when compared with the diabetic isoproterenol group
Summary
Diabetes increases the mortality rate during an acute myocardial infarction (MI) and contributes to the higher morbidity in the post-infarction patients [1]. The therapeutic management of MI mainly relies on the beta blockers, angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers, nitrates, and antithrombotic agents These drugs reinstate blood supply to the myocardial tissue and prevent the apoptotic damage associated with MI [5]. ISO, a non-selective β-adrenoceptor agonist induces MI in rats by a sustained β1 adrenoceptor stimulation that results in an increased lipid peroxidation, generation of free radicals, and exhaustion of the antioxidative defense system. All these isoproterenol-induced physiologic and biochemical alterations cause institution of inflammatory, apoptotic, and necrotic changes in the myocardium and development of an MI. We substantiated the apigenin mediated PPAR-γ stimulation using a pharmacological challenge approach by administering PPAR-γ antagonist before apigenin treatment
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