title: The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.
abstract: This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Thubasni
authors.initials: T
authors.lastname: Kunasegaran
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mohd Rais
authors.initials: MR
authors.lastname: Mustafa
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: dharmani79@um.edu.my.
authors.forename: Dharmani Devi
authors.initials: DD
authors.lastname: Murugan
authors.affiliation: California University of Science and Medicine, California, USA. Electronic address: achikef@calmedu.org.
authors.forename: Francis I
authors.initials: FI
authors.lastname: Achike
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005632:Fructose / Q000633:toxicity; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D000077205:Pioglitazone; D011794:Quercetin / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000804:Angiotensin II; D005632:Fructose; D011794:Quercetin; D000077205:Pioglitazone
keywords: Angiotensin II; Nitric oxide; Pioglitazone; Quercetin; Superoxide anions