N-Acetylcysteine negatively modulates nitric oxide production in endotoxin-treated rats through inhibition of NF-kappaB activation.
N-Acetylcysteine (NAC) has a wide spectrum of biological activities, either related to the ability to increase intracellular thiols or directly acting as an antioxidant. We used an in vivo animal model to study NAC modulation of nitric oxide (NO) production in response to lipopolysaccharide treatment. A comparison was made between NAC and the N-[3-(aminomethyl)benzyl] acetamidine (1400W), an inhibitor of the inducible NO synthase (iNOS). Both inhibit NO production, although NAC lacks any effect if given when iNOS is already induced; this indicates that the decrease of NO generation is not due to an effect on iNOS activity. We found that the DNA binding activity of nuclear transcription factor-kappaB in peripheral blood cells was inhibited by NAC given before lipopolysaccharide, whereas tumor necrosis factor-alpha secretion was not affected.
Rota
Cristina
C
Department of Biomedical Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Bergamini
Stefania
S
Daneri
Francesca
F
Tomasi
Aldo
A
Virgili
Fabio
F
Iannone
Anna
A
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002956:Citrulline / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D002956:Citrulline; D009569:Nitric Oxide; D004247:DNA; D000111:Acetylcysteine