PMID: 293694Nov 1, 1979

Galactosamine-induced sensitization to the lethal effects of endotoxin

Proceedings of the National Academy of Sciences of the United States of America
C GalanosW Reutter

Abstract

Treatment of rabbits, rats, and mice with D-galactosamine increased their sensitivity to the lethal effects of lipopolysaccharide several thousand fold. The susceptibility of the animals was highest when the lipopolysaccharide was injected together with galactosamine and decreased successively when injection was carried out 1, 2, and 3 hr later. Sensitization was absent when the lipopolysaccharide was administered 1 hr before or 4 hr after galactosamine. The onset of lethality after treatment with galactosamine and lipopolysaccharide occurred faster than with lipopolysaccharide alone; usually all animals died 5-9 hr later. The galactosamine-induced sensitization to lipopolysaccharide could be reversed by uridine which is known to inhibit the early biochemical alterations induced by the amino sugar in the hepatocytes. Although galactosamine is known to exhibit hepatotoxic activity inducing ultimate necrosis of the hepatocytes, the data so far suggests that the sensitization to lipopolysaccharide is related only to the early metabolic effects of the hexosamine.

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Related Concepts

Necrosis
Amino Sugars
Drug-Induced Acute Liver Injury
L-Iditol 2-Dehydrogenase
Salmonella
Galactosamine
Lipopolysaccharides
Liver Dysfunction
Drug Augmentation
Hepatocyte

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