TY - JOUR
T1 - The protective effect of apigenin on myocardial injury in diabetic rats mediating activation of the PPAR-γ pathway
AU - Mahajan, Umesh B.
AU - Chandrayan, Govind
AU - Patil, Chandragouda R.
AU - Arya, Dharamvir Singh
AU - Suchal, Kapil
AU - Agrawal, Yogeeta O.
AU - Ojha, Shreesh
AU - Goyal, Sameer N.
N1 - Funding Information:
The authors gratefully acknowledge the financial support received under DBT-Bio-CARe, New Delhi, India to Yogeeta O. Agrawal. The authors also acknowledge the financial support to the research works in the laboratory of Shreesh Ojha from United Arab Emirates University, United Arab Emirates.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
KW - Apigenin
KW - Diabetic cardiac complications
KW - Myocardial infarction
KW - PPAR-γ
KW - Streptozotocin
UR - http://www.scopus.com/inward/record.url?scp=85017147617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017147617&partnerID=8YFLogxK
U2 - 10.3390/ijms18040756
DO - 10.3390/ijms18040756
M3 - Article
C2 - 28375162
AN - SCOPUS:85017147617
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 756
ER -