title: Mechanisms and mediators in hepatic necrosis.
abstract: Necrotic processes may be restricted to individual cell types of the liver or afflict several liver cells sequentially. Noxious agents may induce necrobiosis by different mechanisms of injury. In many instances, however, similar or identical terminal processes are involved, e.g. accumulation of Ca2+ in cytosol or mitochondria, termination of nucleic acid and protein syntheses or membrane damage. Apoptosis may also be a relevant feature of hepatic necrosis. Inhibition of mRNA synthesis and post-translational glycosylations of proteins of the hepatocytes is instrumental in D-galactosamine-induced hepatocellular necrosis. An early event seen after administration of D-galactosamine plus endotoxin is an accumulation of neutrophilic granulocytes in the liver sinusoids. It results from the tumor necrosis factor (TNF)-alpha-induced adhesion of polymorphonuclear leukocytes to the sinusoidal endothelium and the vasoconstriction due to thromboxane A2 that is secreted by activated Kupffer cells. Temporal hypoxia and nutrient deprivation as well as the activation of the granulocytes with release of reactive oxygen species and proteinases appear to be severe consequences. Hypoxia followed by reperfusion (reoxygenation) must be considered as a mechanism of liver cell necrosis producing reactive oxygen species; oxygen radicals were reported to be signals for the activation of nuclear factor kappa B and thereby for the cytotoxicity of cytokines.
authors: Biochemical Institute, University of Freiburg, Germany.
authors: K
authors: K
authors: Decker
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D004731:Endotoxins / Q000494:pharmacology; D005688:Galactosamine / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D004731:Endotoxins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D005688:Galactosamine