Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice

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. Key words: endotoxaemia, flavonoid, lipopolysaccharide, nitric oxide, oxidative stress, quercetin, vascular dysfunction. La quercetine, un flavonoi'de antioxydant alimentaire, possede de fortes proprietes anti-inflammatoires et cytoprotectrices. Ses effets ont ete examines chez un modele animal d'endotoxemie induite par le lipopolysaccharide (LPS) et de dysfonction vasculaire in vivo. Des souris males ICR ont recu une injection de LPS (10 mg/kg; i.p.). La quercetine (50 ou 100 mg/kg) a ete administree par voie intra-gastrique avant ou apres l'administration de LPS. Quinze heures apres l'injection de LPS, les souris manifestaient des signes d'endotoxemie traduits par une hypotension, une tachycardie et des reponses vasculaires reduites aux vasodilatateurs et aux vasoconstricteurs. Les symptomes etaient accompagnes d'une augmentation de l'expression d'iNOS aortique, d'une diminution de l'expression d'eNOS aortique, d'une suppression marquee de l'etat redox du gluthation cellulaire (GSH), d'une augmentation de la production de superoxydes aortiques, d'une augmentation de dialdehyde malonique et de proteines carbonylees, et d'une elevation du rapport nitrate/nitrite urinaire. Le traitement a la quercetine administre soit avant ou apres le LPS preservait la fonction vasculaire car la pression sanguine, le rythme cardiaque et la reponse vasculaire etaient retablis a des niveaux pres de la normale, particulierement lorsque la quercetine etait donnee en prevention. Les effets protecteurs vasculaires etaient associes a une regulation a la hausse de l'expression d'eNOS, a une reduction du stress oxydant et au maintien du ratio redox du GSH sanguin. L'ensemble des resultats suggere un effet benefique de la quercetine dans la prevention et le retablissement du systeme eNOS defaillant et dans l'attenuation du stress oxydant et de la dysfonction vasculaire associes au choc endotoxique chez la souris. Mots-cles: endotoxemie, flavonoi'de, lipopolysaccharide, oxyde nitrique, stress oxydant, quercetine, dysfonction vasculaire. [Traduit par la Redaction]
Introduction It is generally accepted that diets rich in fruit and vegetables protect against cardiovascular diseases (Hertog et al. 1993). Quercetin is one of the most frequently studied dietary flavonoids [...]