title: The mechanism of organ injury in alcoholics: implications for therapy.
abstract: Organ damage due to alcohol abuse includes especially the CNS and the GI tract. The mechanism of liver injury has been studied in depth. Alterations in membrane fluidity, signal transduction, cytochrome, P-450 induction, oxidative stress, acetaldehyde adducts, eicosanoid metabolism, cytoskeletal function, energy metabolism, O2 consumption, microcirculation, Kupffer cell and ito cell activation, immune injury, and gene expression have been documented. Therapeutic implications of these studies include oxandrolone, PTU and colchicine. Pancreatic injury has been studied in vivo and with isolated acini. Amylase release is enhanced directly by ethanol probably by increasing cytosolic Ca2+. Chronic alcohol feeding decreases the CCK receptor sensitivity and affinity for CCK and the pkc response is reduced as is Ca2+ mobilization. Eicosanoids may mediate the damage to the gastric microcirculation. Inhibitors of leukotriene A4 synthesis reduce the ethanol-induced mucosal damage. Exogenous prostaglandins protect the gastric mucosa from ethanol damage and microvascular stasis. In the CNS, alterations induced by ethanol include changes in membrane fluidity and receptor transduction modulation.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: S W
authors.initials: SW
authors.lastname: French
mesh_terms: D000437:Alcoholism / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005756:Gastritis / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000139:chemically induced; D010764:Phosphorylase Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: D000431:Ethanol; D010764:Phosphorylase Kinase; D011493:Protein Kinase C