Cardiovascular complications are the major causes of mortality among diabetic population. Poly(ADPribose) polymerase-1 enzyme (PARP-1) is activated by oxidative stress leading to cellular damage. We investigated the implication of PARP-1 in diabetic cardiac complications. Type 2 diabetes was induced in rats by high fructose-high fat diet and low streptozotocin dose. PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for ten weeks after diabetes induction. At the end of study, surface ECG, blood pressure and vascular reactivity were studied. PARP-1 activity, reduced glutathione (GSH) and nitrite contents were assessed in heart muscle. Fasting glucose, fructosamine, insulin, and tumor necrosis factor alpha (TNIF-alpha) levels were measured in serum. Finally, histological examination and collagen deposition detection in rat ventricular and aortic sections were carried out. Hearts isolated from diabetic animals showed increased PARP-1 enzyme activity compared to control animals while significantly reduced by 4-AB administration. PARP-1 inhibition by 4-AB alleviated cardiac ischemia in diabetic animals as indicated by ECG changes. PARP-1 inhibition also reduced cardiac inflammation in diabetic animals as evidenced by histopathological changes. In addition, 4 -AB administration improved the elevated blood pressure and the associated exaggerated vascular contractility, endothelial destruction and vascular inflammation seen in diabetic animals. Moreover, PARP-1 inhibition decreased serum levels of TNIF-alpha and cardiac nitrite but increased cardiac GSH contents in diabetic animals. However, PARP-1 inhibition did not significantly affect the developed hyperglycemia. Our findings prove that PARP-1 enzyme plays an important role in diabetic cardiac complications through combining inflammation, oxidative stress, and fibrosis mechanisms. (C) 2016 Published by Elsevier B.V.
机构:
King Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21413, Saudi ArabiaKing Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21413, Saudi Arabia
Azhar, Ahmad
El-Bassossy, Hany M.
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King Abdulaziz Univ, Dept Pharmacol, Fac Pharm, Jeddah 21413, Saudi Arabia
Zagazig Univ, Fac Pharm, Dept Pharmacol, Zagazig, EgyptKing Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21413, Saudi Arabia
机构:
UNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADAUNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADA
DAI, S
MCNEILL, JH
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UNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADAUNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADA
机构:
King Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21413, Saudi ArabiaKing Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21413, Saudi Arabia
Azhar, Ahmad
El-Bassossy, Hany M.
论文数: 0引用数: 0
h-index: 0
机构:
King Abdulaziz Univ, Dept Pharmacol, Fac Pharm, Jeddah 21413, Saudi Arabia
Zagazig Univ, Fac Pharm, Dept Pharmacol, Zagazig, EgyptKing Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21413, Saudi Arabia
机构:
UNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADAUNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADA
DAI, S
MCNEILL, JH
论文数: 0引用数: 0
h-index: 0
机构:
UNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADAUNIV BRITISH COLUMBIA, FAC PHARMACEUT SCI, DIV PHARMACOL & TOXICOL, VANCOUVER, BC V6T 1Z3, CANADA