Effect of acute ethanol administration on the intestinal absorption of endotoxin in rats.
BACKGROUND
Endotoxin has been implicated in the pathogenesis and progression of alcoholic liver disease. Not only inactivation of reticuloendothelial function, which reduces clearance of endotoxin, but also an increase in absorption of endotoxin from the intestine may be involved in mechanisms of ethanol-induced endotoxemia. However, it is unclear how ethanol affects absorption of endotoxin from the intestine in vivo.


METHODS
We gave 10 mg/kg of lipopolysaccharides to rats with water (group 1), 5% ethanol (group 2), or 20% ethanol (group 3) using an intubation tube to the stomach. Blood samples were collected and plasma endotoxin levels were measured. We used fluorescence spectrophotometer to examine permeability of the gut to macromolecules (fluorescein isothiocyanate-dextran; 4,000 Da [FD4] or 20,000 Da [FD20]).


RESULTS
Plasma endotoxin levels were not different between group 1 (9 +/- 2 pg/ml) and group 2 (14 +/-3 pg/ml), whereas they significantly increased in group 3 with a peak at 60 min (87 +/- 35 pg/ml). Acute ethanol administration did not affect clearance of endotoxin in rats. Hemorrhagic erosions of the proximal small intestine with epithelial cell loss were observed in group 3 at 4 hr, but no significant histological change was observed at 30 min by light microscopy. Acute ethanol administration (20%) increased the permeability of the small intestine to FD4 and FD20 in 30 min when no hemorrhagic erosions of the proximal small intestine with epithelial cell loss were observed.


CONCLUSIONS
Acute ethanol administration increases intestinal permeability before pathological changes are revealed by light microscopy. Acute ethanol ingestion, especially at high concentrations, facilitates the absorption of endotoxin from rats' small intestine via an increase in intestinal permeability, which may play an important role in endotoxemia observed in alcoholic liver injury.
Tamai
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kato
S
S
Horie
Y
Y
Ohki
E
E
Yokoyama
H
H
Ishii
H
H
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004731:Endotoxins / Q000097:blood*; D000431:Ethanol / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D004731:Endotoxins; D008070:Lipopolysaccharides; D000431:Ethanol