The antagonistic effect of tamoxifen against d-galactosamine/lipopolysaccharide-induced acute liver failure is associated with reactivation of hepatic nuclear factor-κB.
Immunopharmacol Immunotoxicol
; 41(2): 192-198, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30721100
ABSTRACT
Context Tamoxifen (TAM) ameliorates D-galactosamine/lipopolysaccharide (Gal/LPS)-induced acute liver failure (ALF) through its antioxidative effect; thus, this study was designed to determine whether the effectiveness of TAM is related to nuclear factor-κB (NF-κB) reactivation. Materials and methods:
Experimental mice were injected with TAM once daily for 3 consecutive days intraperitoneally (i.p). Twelve hours after pretreatment, Gal/LPS was given to mice (i.p) for ALF induction. In the positive control group, N-acetylcysteine (NAC) was administered immediately after ALF establishment. Except for survival observation, other animals were sacrificed 7 h after Gal/LPS treatment. Survival and hepatic failure were evaluated. For the oxidation assessment, the reduced/oxidized glutathione (GSH/GSSG) ratio and hepatic superoxide dismutase (SOD) activity were analyzed using both colorimetry and Western blotting. Lastly, hepatic NF-κB activation was measured through Western blot analysis of p65 and IκBα.Results:
The results indicated that pretreatment with TAM dramatically attenuated Gal/LPS-induced ALF, as demonstrated by improved survival (70%), decreased transaminase levels, and reversed histopathological manifestation. In addition, the hepatic GSH/GSSG ratio and SOD activity were decreased in the ALF model. However, to some degree, TAM and NAC effectively prevented this undesirable phenomenon in contrast to the ALF model. Western blotting revealed that compared with mice in the ALF model group, mice treated with TAM or NAC showed reactivation of hepatic NF-κB.Conclusions:
Taking the results together with those of other studies, we conclude that TAM may attenuate Gal/LPS-induced ALF by antagonizing oxidative stress through NF-κB reactivation.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Lipopolissacarídeos
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NF-kappa B
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Falência Hepática Aguda
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Galactosamina
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Fígado
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article