title: Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration.
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 anti-lipopolysaccharide 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 anti-lipopolysaccharide 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-alpha 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-alpha or monocyte chemoattractant protein 1 activation during galactosamine-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: M J
authors.initials: MJ
authors.lastname: Czaja
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Ju
authors.forename: E
authors.initials: E
authors.lastname: Alt
authors.forename: P
authors.initials: P
authors.lastname: Schmiedeberg
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D015152:Blotting, Northern; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000378:metabolism; D005688:Galactosamine / Q000008:administration & dosage / Q000633:toxicity; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases