On the pathogenesis of galactosamine hepatitis. Indications of extrahepatocellular mechanisms responsible for liver cell death.
In order to evaluate the pathogenesis of galactosamine hepatitis, the action of galactosamine on mast cells, and alteration in the complement system suring the course of this experimental injury were studied. It has been previously demonstrated that rat livers after colectomy are refractory to galactosamine-induced liver cell necrosis and inflammation. For this reason colectomized animals were used to see whether the biochemical alterations produced by this aminosugar and thought to be responsible for cell death developed. Results showed: 1. galactosamine potently degranulates mast cells in vivo and in vitro, 2. the complement system is a) activated during the course of galactosamine hepatitis, probably by circulating endotoxins, and b) is essential for liver cell death in galactosamine hepatitis, and 3. colectomy does not prevent biochemical changes known to occur during galactosamine metabolism. It is concluded that death of galactosamine-injured liver cells is triggered by extrahepatocellular mechanisms, which lead ultimately to an activated complement system by endotoxins. It is postulated that related mechanism may also occur in viral hepatitis and in fulminant hepatic failure in man.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology*; D003082:Colectomy; D003165:Complement System Proteins / Q000032:analysis; D004731:Endotoxins; D005688:Galactosamine / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009336:Necrosis; D051381:Rats
D004731:Endotoxins; D005688:Galactosamine; D003165:Complement System Proteins