Synergistic action of hepatocyte membrane defect and activated complement system in liver cell death--an experimental approach to fulminant hepatic failure.
The hypothesis was tested whether under the presence of a membrane defect of hepatocytes an activation of the complement system leads to massive liver cell necrosis. Low doses of galactosamine (50, 100, and 200 mg/kg) were administered to rats with and without an additional i.v. injection of sublethal doses of endotoxin (1.5 mg/kg). The latter was done in order to activate the complement system via the C3-bypath. Neither after doses of 50 mg/kg and 100 mg/kg nor after an additional administration endotoxin liver cell necrosis were observed. A dose of 200 mg/kg led to moderate liver cell necrosis, and when administered with endotoxin fulminant hepatic necrosis developed. The explanation was given that only after 200 mg/kg alterations of hepatocytes membranes were present, which prepare liver cells for complement mediated hepatocytolysis. In rats to which 1 g/kg galactosamine was given in addition to endotoxin it was demonstrated by immunohistology that the third component of complement was already fixed on hepatocyte plasma membranes at hour 3 and was accumulated within areas of necrotic liver parenchymal cells at hour 12. Thus, liver cell death is suggested as complement mediated if the membranes are altered. Clinical implications are given in concern of fulminant hepatic failure and an approach to effective treatment regims.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D003176:Complement C3 / Q000032:analysis; D003165:Complement System Proteins / Q000378:metabolism; D004357:Drug Synergism; D004731:Endotoxins / Q000009:adverse effects*; D005688:Galactosamine / Q000009:adverse effects*; D009336:Necrosis; D051381:Rats
D003176:Complement C3; D004731:Endotoxins; D005688:Galactosamine; D003165:Complement System Proteins