Journal
LIFE SCIENCES
Volume 85, Issue 1-2, Pages 54-59Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2009.04.012
Keywords
Flavonol; Diabetes; Endothelium; Superoxide; Relaxation
Funding
- Commission of Higher Education
- Ministry of Education, Thailand
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Aims: Diabetes increases oxidant stress and impairs endothelium-dependent relaxation. We investigated whether the antioxidant 3',4'-dihydroxyflavonol (DiOHF) reduces the release of superoxide (O-2(-)) and preserves endothelial function in aortae from diabetic rats. Main methods: Type-1 diabetes was induced in Sprague-Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.) and vascular reactivity and superoxide generation were assessed in aortic rings using standard organ bath techniques and lucigenin-enhanced chemiluminescence respectively. Key findings: Eight weeks after STZ treatment blood glucose was elevated (39.4 +/- 0.4 mM) compared to citrate treated control rats (5.5 +/- 0.1 mM, P<0.05) and there was an increased aortic generation of O-2(-) (control 670 +/- 101, diabetic 1535 +/- 249 units/mg dry weight, P<0.05). In aortic rings acetylcholine (ACh)-induced relaxation was impaired (R-max control 78 +/- 2, diabetic 66 +/- 3% P<0.01) whereas endothelium-independent relaxation to sodium nitroprusside (SNP) was unaffected (R-max control 100 +/- 1, diabetic 101 +/- 2%). When aortic rings were acutely exposed to DiOHF (10(-5) M) there was a significant reduction in the detection of O-2(-) (control 124 +/- 15, diabetic 165 +/- 21 units/mg, P<0.01) and enhanced relaxation to ACh (R-max control 84 +/- 3, diabetic 87 +/- 3%). Two separate groups of rats (control and diabetic) were treated daily with DiOHF (5 mg/kg i.p.) for 7 days. DiOHF treatment reduced superoxide generation in diabetic aortae (untreated diabetic 1471 +/- 358, DiOHF-treated diabetic 580 +/- 115 units/mg, P<0.05) and enhanced acetylcholine-induced relaxation (R-max untreated diabetic 58 +/- 5. DiOHF-treated diabetic 71 +/- 4%. P<0.05). Significance: DiOHF, acutely in vitro or after 1 week treatment in vivo, reduces oxidant stress and preserves endothelium-dependent relaxation in aortae from diabetic rats. (C) 2009 Elsevier Inc. All rights reserved.
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