The Protective Effect of Apigenin on Myocardial Injury in Diabetic Rats mediating Activation of the PPAR-γ Pathway

• Published in: International journal of molecular sciences 2017-04, Vol.18 (4), p.756
• Main Authors: Mahajan, Umesh B, Chandrayan, Govind, Patil, Chandragouda R, Arya, Dharamvir Singh, Suchal, Kapil, Agrawal, Yogeeta O, Ojha, Shreesh, Goyal, Sameer N
• Format: Article
• Language: English
• Subjects: Activation; Anilides - administration & dosage; Anilides - pharmacology; Animals; Apigenin - administration & dosage; Apigenin - pharmacology; Blood pressure; Blotting, Western; Bundling; Cardiotonic Agents - pharmacology; Cell death; Creatine; Creatine kinase; Creatine Kinase, MB Form - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - prevention & control; Diastolic pressure; Edema; Heart; Heart - drug effects; Heart - physiopathology; Hemodynamics - drug effects; Isoproterenol; L-Lactate dehydrogenase; L-Lactate Dehydrogenase - metabolism; Lactate dehydrogenase; Lactic acid; Male; Myocardial infarction; Myocardial Infarction - chemically induced; Myocardial Infarction - metabolism; Myocardial Infarction - prevention & control; Myocardium; Myocardium - metabolism; Myocardium - pathology; Myonecrosis; Oxidative stress; Peroxisome proliferator-activated receptors; PPAR gamma - antagonists & inhibitors; PPAR gamma - metabolism; Rats; Rats, Wistar; Rodents; Signal Transduction - drug effects; Streptozocin; Ventricle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18040756

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.