Enhanced biliary gamma‐glutamyltransferase excretion following prolonged alcohol consumption in rats

Abstract

In order to study the question of whether chronic ethanol consumption may alter the biliary excretion of gamma-glutamyltransferase (gamma-GT), female rats were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 24 days. Compared to pair-fed controls, the administration of the alcohol-containing diet resulted in an increased biliary excretion of gamma-GT (5.84 +/- 0.73 mU 6 h-1 100 g-1 b.w. vs. 8.82 +/- 0.79, P less than 0.001). This was associated with a corresponding enhanced biliary output of total bile acids. An apparent linear relation between the biliary output rates of gamma-GT and those of total bile acids was observed both in alcohol-fed animals (r = 0.83) and in their pair-fed controls (r = 0.95). In addition, there was a significant increase of gamma-glutamyltransferase activities in the liver homogenate and in liver plasma membranes, both in fractions rich in bile canalicular and basolateral membranes and in those rich in blood sinusoidal site. Serum gamma-glutamyltransferase activities as well as serum bile acid concentrations were also enhanced by 96.8% (P less than 0.001) and 233% (P less than 0.001), respectively. These data show that chronic alcohol consumption enhances hepatic gamma-GT activities, leading to an increased efflux of gamma-GT into the bile and possibly into the blood out of the liver cell. Furthermore, these data suggest the involvement of bile acids with their solubilizing properties for the biliary excretion of gamma-GT.

Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects

“…It seems that bile acids play a major role as natural chemicals solubilizing the GGT, an enzyme that is firmly bound to or tightly embedded in the liver plasma membranes and microsomal membranes. This view is supported by increased serum bile acid levels after experimental chronic alcohol use [298], in line with similar data obtained in patients with ALD [299].…”

“…Patients with alcoholic fatty liver show mostly striking increased GGT activities in the serum, associated with corresponding increases in the liver; these data were reproducible in an animal model of chronic alcohol feeding (Table 6) [295], useful for studying the mechanism of increased serum GGT activities [293,296,297,298,300].…”

“…Prolonged alcohol use increased GGT activities also in the liver plasma membranes, more so in bile canaliculi-enriched ones than in those free of bile canaliculi [296,297]. In other experimental studies, chronic alcohol consumption was found to increase bile flow, biliary GGT excretion, and bile acid output, all parameters that are assessed after cannulation of the bile duct [298]. The relationship between the biliary output of total bile acids and GGT was plotted against each other, and this showed an apparent linear relationship between both parameters in alcohol-fed animals, as well as in their pair-fed controls [298].…”

“…In other experimental studies, chronic alcohol consumption was found to increase bile flow, biliary GGT excretion, and bile acid output, all parameters that are assessed after cannulation of the bile duct [298]. The relationship between the biliary output of total bile acids and GGT was plotted against each other, and this showed an apparent linear relationship between both parameters in alcohol-fed animals, as well as in their pair-fed controls [298]. It seems that bile acids play a major role as natural chemicals solubilizing the GGT, an enzyme that is firmly bound to or tightly embedded in the liver plasma membranes and microsomal membranes.…”