Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas.
The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress.
Machha
Ajay
A
Department of Pharmacology, University of Malaya, Kuala Lumpur 50603, Malaysia. ajayphd_2006@yahoo.com
Achike
Francis I
FI
Mustafa
Ali Mohd
AM
Mustafa
Mohd Rais
MR
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005419:Flavonoids / Q000627:therapeutic use*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D011921:Rats, Inbred WKY; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects
D000975:Antioxidants; D001786:Blood Glucose; D005419:Flavonoids; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011794:Quercetin