Effect of Chronic Ethanol Administration on
Gamma-Glutamyltransferase Activities in Plasma and in
Hepatic Plasma Membranes of Male and Female Rats

Lahrichi, M.; Ratanasavanh, Damrong; Galteau, Marie‐Madeleine; Siest, Gérard

doi:10.1159/000459109

Cited by 21 publications

(4 citation statements)

References 22 publications

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“…Notably, the magnitude of hepatic GGT increase was different between these three studies and was related to whether the whole liver or the hepatic plasma membrane fraction, the predominant location of liver GGT, was evaluated. The lack of concordance between liver and serum GGT activities is not surprising, given the low baseline activity (Lahrichi et al 1982) and exceptionally short circulating half-life of GGT in the rat (Boyd 1983; Huseby 1992; Loeb 1999).…”

Section: Hepatic Effects Of Dme Induction In Animalsmentioning

confidence: 99%

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

et al. 2010

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Hepatic drug-metabolizing enzyme (DME) induction is an adaptive response associated with changes in preclinical species; this response can include increases in liver weight, hepatocellular hyperplasia and hypertrophy, and upregulated tissue expression of DMEs. Effects of DME induction on clinical pathology markers of hepatobiliary injury and function in animals as well as humans are not well established. This component of a multipart review of the comparative pathology of xenobiotically mediated induction of hepatic metabolizing enzymes reviews pertinent data from retrospective and prospective preclinical and clinical studies. Particular attention is given to studies with confirmation of DME induction and concurrent evaluation of liver and/or serum hepatobiliary marker enzyme activities and histopathology. These results collectively indicate that in the rat, when histologic findings are limited to hepatocellular hypertrophy, DME induction is not expected to be associated with consistent or substantive changes in serum or plasma activity of hepatobiliary marker enzymes such as alanine aminotransferase, alkaline phosphatase, and gamma glutamyltransferase. In the dog and the monkey, published studies also do not demonstrate a consistent relationship across DME-inducing agents and changes in these clinical pathology parameters. However, increased liver alkaline phosphatase or gamma glutamyltransferase activity in dogs treated with phenobarbital or corticosteroids suggests that direct or indirect induction of select hepatobiliary injury markers can occur both in the absence of liver injury and independently of induction of DME activity. Although correlations between tissue and serum levels of these hepatobiliary markers are limited and inconsistent, increases in serum/plasma activities that are substantial or involve changes in other markers generally reflect hepatobiliary insult rather than DME induction. Extrahepatic effects, including disruption of the hypothalamic-pituitary-thyroid axis, can also occur as a direct outcome of hepatic DME induction in humans and animals. Importantly, hepatic DME induction and associated changes in preclinical species are not necessarily predictive of the occurrence, magnitude, or enzyme induction profile in humans.

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Section: Hepatic Effects Of Dme Induction In Animalsmentioning

confidence: 99%

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

et al. 2010

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“…activity is present in the serum of both humans [l-61 and experimental animals 14, 7-10], and its determination is of particular clinical interest in patients with disorders of the biliary tract and the liver [I] including alcohol-related liver disease [24]. There is general belief that serum y-GT activity is derived primarily from the liver rather than from other organs such as the pancreas or kidneys, although the latter organs exhibit a much higher enzymic activity of y-GT than the liver [3, 51. Chronic alcohol consumption has been shown to provoke increased y-GT activities not only in the serum but also in the liver of both man [2-6, I 1-1 51 and experimental animals [4,[7][8][9][10][16][17][18][19]. It is unclear, however, whether chronic alcohol consumption changes the release of y-GT from the liver cell into the blood, which may proceed through the sinusoidal site of the liver plasma membrane, since quantitative assessment of the latter process is difficult to establish in the living organism.…”

Section: Introductionmentioning

confidence: 99%

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

Teschke

Krukenberg

Stremmel

et al. 1987

Eur J Clin Investigation

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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.

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“…However, little is known of the reactivity between the GSH metabolite and AcH. As there are increases of ~,-glutamyltranspeptidase (y-GTP) activity in the liver or the plasma after chronic ethanol consumption [19][20][21], the present study was carried out in vitro to examine the reactivity of AcH with GSH and its degradation metabolites, and the significances of GSH metabotites, especially in kidney, during acute ethanol intoxication are discussed.…”

Section: Introductionmentioning

confidence: 99%

Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown byγ-glutamyltranspeptidase

1985

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Glutathione and its metabolites were examined for reactivity to acetaldehyde. When acetaldehyde was incubated with glutathione alone, there was only a slight decrease of acetaldehyde, while an apparently equimolar reaction between acetaldehyde and free sulfhydryl was observed with the addition of gamma-glutamyltranspeptidase. Cysteinylglycine, the first metabolite in the glutathione breakdown by gamma-glutamyltranspeptidase, showed a rapid and equimolar reactivity to acetaldehyde and such was comparable to the reaction seen with L-cysteine or D-penicillamine. In light of the chemical structure, cysteinylglycine probably conjugates with acetaldehyde to form thiazolidinecarboxylic acid derivatives, 2-methyl-thiazolidine-4-carbonyl-glycine, and if so, the alteration of glutathione metabolism by acetaldehyde during ethanol intoxication warrants further attention.

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Effect of Chronic Ethanol Administration on Gamma-Glutamyltransferase Activities in Plasma and in Hepatic Plasma Membranes of Male and Female Rats

Cited by 21 publications

References 22 publications

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

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

Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown byγ-glutamyltranspeptidase

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