Lipopolysaccharide augments the in vivo lethal action of doxorubicin against mice via hepatic damage.
Clin Exp Immunol
; 151(2): 334-40, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-18062793
ABSTRACT
The effect of lipopolysaccharide (LPS) on the in vivo lethal action of doxorubicin (DOX) against mice was studied. DOX killed LPS-pretreated mice much earlier than untreated mice, and exhibited a stronger toxic action against LPS-pretreated mice. DOX-induced lethality in LPS-pretreated mice was due to severe hepatic damage, but there were no significant lesions in the heart, kidney and lung. Hepatic lesions were accompanied by caspase 3-positive cells and fragmented DNA-positive cells, suggesting the involvement of apoptosis. DOX induced the production of a high level of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in LPS-pretreated mice, but not in non-treated mice. The DOX-induced lethality was prevented significantly by anti-IFN-gamma antibody, but not anti-TNF-alpha antibody. Administration of recombinant IFN-gamma in place of LPS augmented definitively the DOX-induced lethality. LPS augmented the DOX-induced lethality in TNF-alpha-deficient mice. Taken together, LPS was suggested to enhance DOX-induced IFN-gamma production and augment the in vivo lethal action via hepatic damage.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Lipopolissacarídeos
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Doença Hepática Induzida por Substâncias e Drogas
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Antibióticos Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Clin Exp Immunol
Ano de publicação:
2008
Tipo de documento:
Article