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Clin Exp Immunol. 2008 Feb;151(2):334-40. Epub 2007 Dec 6.

Lipopolysaccharide augments the in vivo lethal action of doxorubicin against mice via hepatic damage.

Author information

  • 1Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. yokochi@aichi-med-u.ac.jp

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.

PMID:
18062793
[PubMed - indexed for MEDLINE]
PMCID:
PMC2276946
Free PMC Article
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