Glycine prevents alcohol-induced liver injury by decreasing alcohol in the rat stomach.
OBJECTIVE
Inactivation of Kupffer cells prevents alcohol-induced liver injury, and hypoxia subsequent to a hypermetabolic state caused by activated Kupffer cells probably is involved in the mechanism. Glycine is known to prevent hepatic reperfusion injury. The purpose of this study was to determine whether glycine prevents alcohol-induced liver injury in vivo.


METHODS
Male Wistar rats were exposed to ethanol (10-12 g.kg-1.day-1) continuously for up to 4 weeks via an intragastric feeding protocol. The effect of glycine on the first-pass metabolism of ethanol was also examined in vivo, and the effect on alcohol metabolism was estimated specifically in perfused liver.


RESULTS
Glycine decreased ethanol concentrations precipitously in urine, breath, peripheral blood, portal blood, feces, and stomach contents. Serum aspartate amino-transferase levels were elevated to 183 U/L after 4 weeks of ethanol-treatment. In contrast, values were significantly lower in rats given glycine along with ethanol. Hepatic steatosis and necrosis also were reduced significantly by glycine. Glycine dramatically increased the first-pass elimination of ethanol in vivo but had no effect on alcohol metabolism in the perfused liver.


CONCLUSIONS
Glycine minimizes alcohol-induced liver injury in vivo by preventing ethanol from reaching the liver by activating first-pass metabolism in the stomach.
Iimuro
Y
Y
Department of Pharmacology, University of North Carolina at Chapel Hill, USA.
Bradford
B U
BU
Forman
D T
DT
Thurman
R G
RG
D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001711:Biotransformation / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D005235:Fatty Liver, Alcoholic / Q000517:prevention & control; D005753:Gastric Mucosa / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*
D000431:Ethanol; D001219:Aspartate Aminotransferases; D005998:Glycine