title: Mechanisms of alcoholic liver injury.
abstract: There have been numerous recent advances in the understanding of the mechanisms of alcoholic liver disease pathogenesis. Endotoxin-induced Kupffer cell activation plays a role in cytokine-mediated inflammatory changes in the liver, and this can be blocked by a diet high in saturated fat, by a diet containing lactobacillus, which does not produce endotoxin, by neomycin antibiotic sterilization of the gut, by eliminating Kupffer cells, or by removing tumour necrosis factor-alpha with antibody or by using tumour necrosis factor-alpha knockout mice. The fatty liver component is mainly the result of the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox shift to the reduced state by ethanol oxidation generation of reduced nicotinamide adenine dinucleotide, although this too can be blocked by a diet high in saturated fat. Hepatocytic enlargement occurs due to ethanol-induced inhibition of the ubiquitin-proteasome pathway of cytoplasmic protein degradation and the retention of oxidized proteins in hepatocytes. The liver is scarred by stellate cells that have been activated by inflammatory cytokines and growth factors produced by activated Kupffer cells, and by bile ductule metaplasia. Mallory bodies and balloon cell degeneration develop through the ethanol-induced oxidative stress-protein kinase activation pathway, inhibition of phosphatase activity and inhibition of the ubiquitin-proteasome pathway.
authors.affiliation: Harbor-UCLA Medical Center, Torrance, USA. FRENCH@AFP76.HUMC.EDU
authors.forename: S W
authors.initials: SW
authors.lastname: French
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha