ABSTRACT
Increased hepatic gamma-glutamyltransferase (GGT) activity following chronic ethanol consumption has been attributed to enzyme induction, dietary carbohydrate imbalance, and/or to hepatic cell damage. In this study, hepatic GGT activity was increased in rats consuming ethanol (35% of kcals) in a high fat (35% of kcals) diet compared to pair fed and ad lib. fed high fat controls (P less than or equal to 0.01), but no enhancement of activity was observed in those rats consuming ethanol on low fat (11% of kcals) diets. The high-fat-ethanol group also had increased hepatic lipid (P less than or equal to 0.01) and decreased glutathione levels (P less than or equal to 0.05) compared to their ad lib. fed control group. In rats that had ethanol removed from their diet for the final 4 weeks of the 12-week dietary treatment period, levels of GGT, lipid or glutathione were not different from control values. Histochemical evaluation of hepatic GGT activity showed increases associated with centrolobular lipid accumulation in ethanol-fed rats consuming a high fat diet. The cause of the increase in hepatic GGT activity could not be determined from this experiment. However, increased microsomal enzyme activity did not appear to be related to GGT activity. It is suggested that cellular damage following increased lipid accumulation, depletion of hepatic glutathione, or changes in biliary flow may be associated with the increased GGT activity.
Subject(s)
Alcoholism/enzymology , Dietary Fats/metabolism , Liver/enzymology , gamma-Glutamyltransferase/metabolism , Animals , Bile Ducts, Intrahepatic/enzymology , Body Weight , Glutathione/metabolism , Lipid Metabolism , Liver/anatomy & histology , Male , Organ Size , RatsSubject(s)
Ethanol/adverse effects , Liver Neoplasms/etiology , Alcohol Drinking , Animals , Carcinoma, Hepatocellular/etiology , Cell Membrane/drug effects , Cocarcinogenesis , DNA/metabolism , Humans , In Vitro Techniques , Liver Cirrhosis, Alcoholic/complications , Liver Cirrhosis, Alcoholic/etiology , Liver Neoplasms, Experimental/etiology , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Mixed Function Oxygenases/metabolism , Nutritional Physiological PhenomenaABSTRACT
In this study, the effect of chronic ethanol ingestion on the modification of the postinitiation phase of hepatocarcinogenesis was examined. Hepatic lesions were initiated in Sprague-Dawley rats by administration of 10 doses of aflatoxin B1 (AFB1) over a 2-week period. Following a week of acclimation rats were fed ethanol (35% of caloric intake) in low fat (11% of calories) or high fat (35% of calories) AIN-76-based liquid diets according to a unique feeding regime for 12 weeks. The effect of ethanol on the development of hepatic gamma-glutamyltransferase (GGT)-positive foci and on nutrient status was evaluated. Only those rats consuming ethanol with a high fat diet developed fatty livers, but all those consuming ethanol had low hepatic vitamin A and glutathione levels compared to pair-fed and ad libitum-fed controls. Despite these changes, no effect of ethanol consumption on the formation of GGT-positive foci was observed. Rats fed a high fat diet had an increased number and size of foci compared to rats on a low fat diet (P less than or equal to 0.01). It was concluded that despite these effects of ethanol on several physiological parameters, modification of the development of presumptive preneoplastic hepatic foci was not affected.
