title: Metabolic fate of endotoxin and blood tumour necrosis factor levels in rats with acute and chronic alcohol loading.
abstract: To investigate the metabolic fate of endotoxin in alcoholics and its possible relationship to cytokines and liver injury, we administered a low-dose radiolabelled endotoxin to rats given alcohol in various conditions and studied the organ distribution of endotoxin and measured plasma levels of tumour necrosis factor (TNF). In the chronic alcohol-fed rats (Lieber-DeCarli liquid diets for 6 weeks) 3H-endotoxin was rapidly cleared by the liver and excreted into faeces. However, the endotoxin clearance was decreased after an acute ethanol load to rats (5 mg/g body wt ethanol i.p.) or in the chronic ethanol-fed rats with an additional 5 mg/g body wt ethanol load. Plasma TNF was not elevated in the control or in the acute ethanol load rats, slightly elevated in the chronic ethanol-fed rats and markedly elevated in the chronic ethanol-fed rats with an additional high-dose ethanol load. Serum GPT was elevated only in the chronic ethanol-fed rats with an additional high-dose ethanol. In conclusion, an additional administration of a high dose ethanol to chronic alcohol-fed rats led to decrease of endotoxin clearance and elevation of plasma TNF, which may play an important role in the pathogenesis of alcoholic hepatitis.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Kitano
authors.forename: M
authors.initials: M
authors.lastname: Morimura
authors.forename: E
authors.initials: E
authors.lastname: Kikuchi
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Tsujita
authors.forename: K
authors.initials: K
authors.lastname: Kinoshita
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Tsujii
mesh_terms: D000435:Alcoholic Intoxication / Q000097:blood / Q000378:metabolism*; D000437:Alcoholism / Q000097:blood / Q000378:metabolism*; D000818:Animals; D004731:Endotoxins / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D012475:Salmonella; D014018:Tissue Distribution; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium