title: Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice.
abstract: Quercetin, a dietary antioxidant flavonoid, possesses strong anti-inflammatory and cytoprotective activities. The effects were investigated in an animal model of lipopolysaccharide (LPS)-induced endotoxaemia and vascular dysfunction in vivo. Male ICR mice were injected with LPS (10 mg/kg; i.p.). Quercetin (50 or 100 mg/kg) was intragastrically administered either before or after LPS administration. Fifteen hours after LPS injection, mice were found in endotoxaemic condition, as manifested by hypotension, tachycardia, and blunted vascular responses to vasodilators and vasoconstrictor. The symptoms were accompanied by increased aortic iNOS protein expression, decreased aortic eNOS protein expression, marked suppression of cellular glutathione (GSH) redox status, enhanced aortic superoxide production, increased plasma malodialdehyde and protein carbonyl, and elevated urinary nitrate/nitrite. Treatment with quercetin either before or after LPS preserved the vascular function, as blood pressure, heart rate, vascular responsiveness were restored to near normal values, particularly when quercetin was given as a preventive regimen. The vascular protective effects were associated with upregulation of eNOS expression, reduction of oxidative stress, and maintained blood GSH redox ratio. Overall findings suggest the beneficial effect of quercetin on the prevention and restoration of a failing eNOS system and alleviation of oxidative stress and vascular dysfunction against endotoxin-induced shock in mice.
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. upa_ku@kku.ac.th
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
authors.forename: Kwanjit
authors.initials: K
authors.lastname: Sompamit
authors.forename: Patchareewan
authors.initials: P
authors.lastname: Pannangpetch
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.forename: Wanida
authors.initials: W
authors.lastname: Donpunha
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D019446:Endotoxemia / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005978:Glutathione / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D012772:Shock, Septic / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D015854:Up-Regulation; D014657:Vasculitis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D008070:Lipopolysaccharides; D011794:Quercetin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D005978:Glutathione