GLYCINE PREVENTS ALCOHOL-INDUCED LIVER-INJURY BY DECREASING ALCOHOL IN THE RAT STOMACH

Background & Aims: Inactivation of Kupffer cells prevents alcohol-indu ced liver injury, and hypoxia subsequent to a hypermetabolic state cau sed 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 ethano l (10-12 g . kg(-1). day(-1)) continuously for up to 4 weeks via an in tragastric feeding protocol. The effect of glycine on the first-pass m etabolism of ethanol was also examined in vivo, and the effect on alco hol metabolism was estimated specifically in perfused liver. Results: Glycine decreased ethanol concentrations precipitously in urine, breat h, peripheral blood, portal blood, feces, and stomach contents, Serum aspartate aminotransferase levels were elevated to 183 U/L after 4 wee ks of ethanol-treatment. In contrast, values were significantly lower in rats given glycine along with ethanol. Hepatic steatosis and necros is also were reduced significantly by glycine. Glycine dramatically in creased the first-pass elimination of ethanol in vivo but had no effec t on alcohol metabolism in the perfused liver. Conclusions: Glycine mi nimizes alcohol-induced liver injury in vivo by preventing ethanol fro m reaching the liver by activating first-pass metabolism in the stomac h.