Quercetin prevents oxidative stress and NF-kappaB activation in gastric mucosa of portal hypertensive rats.
The present study was designed to investigate the effects of quercetin on oxidative stress and activation of nuclear factor kappa B (NF-kappaB) in an experimental model of portal hypertensive gastropathy induced by partial portal vein ligation (PPVL). Portal pressure was significantly elevated in PPVL rats. Transaminase and alkaline phosphatase activities were not significantly modified, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. The cytosolic concentration of thiobarbituric acid reactive substances and the lipoperoxidation measurement by chemiluminiscence were significantly increased. Superoxide dismutase activity in gastric mucosa was significantly reduced. Portal hypertensive gastropathy induced a marked activation of NF-kappaB, accompanied by a decrease in IkappaB protein levels and a significant induction of nitric oxide synthase (iNOS) protein. Administration of quercetin markedly alleviated histological abnormalities and inhibited oxidative stress and NF-kappaB activation. IkappaB decrease and induction of iNOS protein were partially prevented by quercetin. Quercetin treatment, by abolishing the NF-kappaB signal transduction pathway, may block the production of noxious mediators involved in the pathogenesis of portal hypertensive gastropathy.
Moreira
Andrea J
AJ
Universidade Federal de Rio Grande do Sul and Universidade Luterana do Brasil, Brazil.
Fraga
Christina
C
Alonso
María
M
Collado
Pilar S
PS
Zetller
Claudio
C
Marroni
Claudio
C
Marroni
Norma
N
González-Gallego
Javier
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000473:pathology*; D020672:I-kappa B Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; D011794:Quercetin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D000637:Transaminases