Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat.
We investigated the effects of glutamine on markers of oxidative stress, nuclear factor kappaB (NF-kappaB) activation, and pro-inflammatory mediators in a rat model of experimental colitis induced by intracolonic administration of 7% acetic acid. Glutamine (25 mg/kg) was given by rectal route 48 and 24h before acetic acid instillation. Glutamine significantly reduced gross damage and histopathological scores, and partially prevented the decrease of anal pressure observed in the animals receiving acetic acid. Increases in the cytosolic concentration of TBARS and hydroperoxide-initiated chemiluminescence were significantly prevented in glutamine-treated animals. Acetic acid instillation induced a marked increase of the NF-kappaB p65 subunit expression in the nucleus and resulted in significant changes in the cytosolic protein level of IkappaB kinases (IKKalpha and IKKbeta) and the non-phosphorylated form of the inhibitor IkappaBalpha. Protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were significantly increased. All these effects were partially prevented by administration of glutamine. It is concluded that the anti-inflammatory activity of glutamine in a rat model of acetic acid-induced colitis may be mediated, at least in part, by inhibition of the expression of certain pro-inflammatory mediators which are regulated by the oxidative stress-sensitive NF-kappaB signalling pathway.
Fillmann
Henrique
H
Universidade Luterana do Brasil, Hospital de Clinicas Porto Alegre, Brazil.
Kretzmann
Nelson A
NA
San-Miguel
Beatriz
B
Llesuy
Susana
S
Marroni
Norma
N
González-Gallego
Javier
J
Tuñón
María J
MJ
D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005973:Glutamine / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D007155:Immunologic Factors; D016328:NF-kappa B; D005973:Glutamine; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D019342:Acetic Acid