Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration

Mark J. Czaja, Jun Xu, Yue Ju, Elaine Alt, Phyllis Schmiedeberg

Research output: Contribution to journalArticle

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Abstract

Endogenous lipopolysaccharide has been implicated as a cofactor in the hepatocellular injury and death resulting from toxic liver injury. To prevent this lipopolysaccharide-induced injury and to further understand the mechanism of this effect, an antilipopolysaccharide antibody was administered to rats in which toxic hepatocellular injury was induced. Rats were given the hepatotoxin galactosamine together with an isotypic control antibody B55 or the antilipopolysaccharide antibody E5. E5 treatment resulted in reductions of serum AST levels of 43% at 36 hr (p < 0.02) and 60% at 48 hr (NS) after galactosamine administration. These decreases in AST values were accompanied by diminished histological evidence of injury and inflammation. In carbon tetrachloride-induced liver injury, E5 similarly reduced serum AST levels at 36 and 48 hr by 47% (p < 0.04) and 54% (p < 0.03), respectively. E5 treatment was equally effective in reducing AST levels 48 hr after administration of carbon tetrachloride, whether the initial dose of antibody was given 1 hr before or 3 or 6 hr after the administration of this toxin. To understand the mechanism of this E5 effect, the activation of the toxic cytokine tumor necrosis factor-α and the chemotactic cytokine monocyte chemoattractant protein 1 was examined by Northern-blot analysis of RNA from rat livers after galactosamine-induced injury and treatment with B55 or E5. Despite E5's efficacy in reducing hepatocellular damage, E5 treatment did not affect the timing or magnitude of tumor necrosis factor-α or monocyte chemoattractant protein 1 activation during galactosamine-induced injury. These data suggest that antibody neutralization of lipopolysaccharide may be an effective therapy for toxic liver injury and that the mechanism of this effect is not through the prevention of cytokine expression.

Original languageEnglish (US)
Pages (from-to)1282-1289
Number of pages8
JournalHepatology
Volume19
Issue number5
StatePublished - May 1994

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Neutralizing Antibodies
Lipopolysaccharides
Hepatocytes
Galactosamine
Wounds and Injuries
Poisons
Carbon Tetrachloride
Chemokine CCL2
Liver
Antibodies
Tumor Necrosis Factor-alpha
Cytokines
Serum
Chemokines
Northern Blotting
RNA
Inflammation

ASJC Scopus subject areas

  • Hepatology

Cite this

Czaja, M. J., Xu, J., Ju, Y., Alt, E., & Schmiedeberg, P. (1994). Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. Hepatology, 19(5), 1282-1289.

Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. / Czaja, Mark J.; Xu, Jun; Ju, Yue; Alt, Elaine; Schmiedeberg, Phyllis.

In: Hepatology, Vol. 19, No. 5, 05.1994, p. 1282-1289.

Research output: Contribution to journalArticle

Czaja, MJ, Xu, J, Ju, Y, Alt, E & Schmiedeberg, P 1994, 'Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration', Hepatology, vol. 19, no. 5, pp. 1282-1289.
Czaja, Mark J. ; Xu, Jun ; Ju, Yue ; Alt, Elaine ; Schmiedeberg, Phyllis. / Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. In: Hepatology. 1994 ; Vol. 19, No. 5. pp. 1282-1289.
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