Low-dose ethanol attenuates gut ischemia/reperfusion-induced liver injury in rats via nitric oxide production.
OBJECTIVE
The acute administration of low-dose ethanol was demonstrated to attenuate liver injury elicited by gut ischemia/reperfusion (I/R). Nitric oxide (NO) has been found to be a modulator of adhesive interactions between leukocytes, platelets, and endothelial cells, but there has been much controversy about the effects of ethanol on NO regulation. The objective of this study was to investigate the role of NO in ethanol-reduced hepatic microvascular dysfunction elicited by gut I/R.


METHODS
Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and non-perfused sinusoids (NPS). Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, ethanol (10%, 1 g/kg) was administered before ischemia.


RESULTS
Gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma ALT activities; all of which were attenuated by pretreatment with ethanol or an NO donor. Gut I/R caused the apoptosis of hepatocytes, which was prevented by pretreatment with ethanol. Pretreatment with an NO synthase inhibitor diminished the protective effects of ethanol. The administration of ethanol increased plasma nitrite/nitrate levels.


CONCLUSIONS
These results suggest that low-dose ethanol attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential liver injury by increasing sinusoidal NO levels.
Horie
Yoshinori
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Yamagishi
Yoshiyuki
Y
Kato
Shinzo
S
Kajihara
Mikio
M
Kimura
Hiroyuki
H
Ishii
Hiromasa
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D051263:D-Alanine Transaminase; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D000431:Ethanol / Q000008:administration & dosage*; D020287:In Situ Nick-End Labeling; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology; D008102:Liver Circulation / Q000502:physiology; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D009569:Nitric Oxide; D000431:Ethanol; D004247:DNA; D000410:Alanine Transaminase; D051263:D-Alanine Transaminase