A part of this study was presented at the 38th Meeting of the American Association for the Study of Liver Diseases in Chicago.
Endotoxin-induced hypercoagulability: A possible aggravating factor of alcoholic liver disease†
Article first published online: 5 DEC 2005
Copyright © 1989 American Association for the Study of Liver Diseases
Volume 9, Issue 6, pages 846–851, June 1989
How to Cite
Arai, M., Nakano, S., Okuno, F., Hirano, Y., Sujita, K., Kobayashi, T., Ishii, H. and Tsuchiya, M. (1989), Endotoxin-induced hypercoagulability: A possible aggravating factor of alcoholic liver disease. Hepatology, 9: 846–851. doi: 10.1002/hep.1840090609
- Issue published online: 5 DEC 2005
- Article first published online: 5 DEC 2005
- Manuscript Accepted: 17 OCT 1988
- Manuscript Received: 10 FEB 1988
- Ministry of Education of Japan. Grant Numbers: 61750359, 62570338
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 < 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. Therefore, the results from the present study indicate that chronic ethanol consumption potentiates endotoxin-induced organ injury and that hypersensitive activity to endotoxin of the coagulation-fibrinolysis system after chronic ethanol consumption may, at least in part, pathogenically contribute to the aggravation of organ injury.