Ethanol modulates gut ischemia/reperfusion-induced liver injury in rats.
Whereas both ethanol and gut ischemia/reperfusion (I/R) are known to alter hepatic microvascular function, little is known about the influence of ethanol consumption on the hepatic microvascular responses to I/R. The objective of this study was to determine whether acute ethanol administration exacerbates the hepatic microvascular dysfunction induced by gut I/R. Rats were exposed to gut ischemia for 30 min followed by reperfusion. Intravital videomicroscopy was used to monitor leukocyte recruitment and the number of nonperfused sinusoids (NPS). Plasma alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha), and endotoxin concentrations were monitored. In separate experiments, ethanol was administered 15 min or 24 h before gut ischemia. In control rats, gut I/R increased the number of stationary leukocytes and NPS. It also elevated the plasma ALT, TNF-alpha, and endotoxin with a corresponding increase in intestinal mucosal permeability. Low-dose ethanol consumption 15 min before gut ischemia blunted the gut I/R-induced leukostasis and elevations in plasma TNF-alpha and ALT. However, high-dose ethanol consumption aggravated the gut I/R-induced increases in leukostasis and increases in plasma endotoxin and ALT. When ethanol was administered 24 h before, high-dose ethanol aggravated the gut I/R-induced hepatocellular injury, but low-dose ethanol did not have any effects on it. These results suggest that low-dose ethanol consumption shortly before gut ischemia attenuates the hepatic inflammatory responses, microvascular dysfunction, and hepatocellular injury elicited by gut I/R, whereas high-dose ethanol consumption appears to significantly aggravate these gut I/R-induced responses.
Yamagishi
Yoshiyuki
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, 160-8582 Japan.
Horie
Yoshinori
Y
Kato
Shinzo
S
Kajihara
Mikio
M
Tamai
Hironao
H
Granger
D Neil
DN
Ishii
Hiromasa
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007962:Leukocytes / Q000473:pathology; D008099:Liver / Q000098:blood supply*; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D000410:Alanine Transaminase