title: Endotoxin-induced hypercoagulability: a possible aggravating factor of alcoholic liver disease.
abstract: The present experiments were designed to study the effect of chronic ethanol consumption on endotoxin toxicity. The intravenous injection of endotoxin produced a more pronounced increase of serum AST and ALT activities in chronic ethanol-fed rats, when compared to controls. The activities of hepatic mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, were also distinctly decreased by endotoxin treatment in chronic ethanol-fed rats. Consistent with these biochemical alterations, light and electron microscopic examinations revealed severe liver injury after endotoxin injection in chronic ethanol-fed rats. Furthermore, the increase of blood BUN and creatinine levels accompanied by the degeneration of the renal tubulus and slight infiltration of neutrophils into the glomerule were produced by endotoxin treatment and were more conspicuous in chronic ethanol-fed rats than controls. Therefore, the biochemical and histological evidence indicates that endotoxin markedly potentiates organ injury after chronic ethanol consumption. In addition, a more pronounced decrease in blood antithrombin III activity accompanied by an increase in fibrin degradation product level in blood was recognized in chronic ethanol-fed rats receiving endotoxin, when compared to controls receiving endotoxin. This increase of blood fibrin degradation product level correlated well with the decrease of antithrombin III activity (r = -0.6116; p less than 0.005). These findings of blood antithrombin III activity and fibrin degradation product level indicate that the coagulation-fibrinolysis system is more activated by endotoxin treatment after chronic ethanol consumption. Furthermore, the activation of the coagulation-fibrinolysis system was well correlated with biochemical and histological alterations representing hepatorenal involvement.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Central Clinical Laboratory, School of Medicine, University of Occupational and Environmental Health, Kitakyushu-City, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: S
authors.initials: S
authors.lastname: Nakano
authors.forename: F
authors.initials: F
authors.lastname: Okuno
authors.forename: Y
authors.initials: Y
authors.lastname: Hirano
authors.forename: K
authors.initials: K
authors.lastname: Sujita
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001777:Blood Coagulation; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003576:Electron Transport Complex IV / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism / Q000633:toxicity*; D005342:Fibrinolysis; D006207:Half-Life; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D004731:Endotoxins; D003404:Creatinine; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase