The effect of chronic ethanol consumption and variations in dietary protein content on microsomal drug metabolism were studied in rats pair-fed liquid diets containing 10, 20, ro 30% dietary protein with or without ethanol. In vitro drug metabolism was measured by aminopyrine breath tests and aminopyrine blood elimination kinetics. In vitro drug metabolism was assessed by measuring aminopyrine N-demethylase activity in the hepatic microsomal fraction. The rate of elimination of aminopyrine in vivo was increased in all ethanol-fed animals (p less than 0.05) regardless of the protein content of the diet. Animals receiving 10 or 20% protein diets with ethanol showed a 36% increase in drug elimination over pair-fed controls as compared to a 17% increase in drug elimination over controls in animals receiving 30% protein diets. Microsomal aminopyrine N-demethylase activities were similar in ethanol/fed animals and pair-fed controls. Cytochrome P-450 content was increased in all ethanol-fed animals (p less than 0.05) but the increase was not dependent on dietary protein content. These results indicate that the effect of chronic ethanol feeding in enhancing drug metabolism in vivo is influenced by the dietary protein content.

Alcoholism↗

PubMedDate not supplied

Effect of dihydrotestosterone on rat liver alcohol dehydrogenase activity.

Castration was previously demonstrated to result in an increase in liver alcohol dehydrogenase and in rates of ethanol elimination in male rats. In this study, the effect of dihydrotestosterone, which is a more potent androgen than testosterone in the rat, was determined on liver alcohol dehydrogenase and ethanol elimination in the castrated rat. Dihydrotestosterone was found to be a substrate of liver alcohol dehydrogenase in the reductive direction and a competitive inhibitor of ethanol oxidation by the enzyme. Also, the administration of a single dose of dihydrotestosterone inhibited liver alcohol dehydrogenase 4 hr after the injection, but this effect was not persistent at later intervals following injection. This transient in vivo inhibition of liver alcohol dehydrogenase was associated with a delay in ethanol elimination. The microsomal ethanol-oxidizing enzyme system was found to play no role in the changes in ethanol elimination observed after castration and dihydrotestosterone administration since its activity remained unchanged. These studies provide further evidence of an effect of androgenic steroids on liver alcohol dehydrogenase activity and ethanol metabolism.

Alcohol Dehydrogenase↗

PubMedDate not supplied

Effect of chronic ethanol feeding on hepatic mitochondria in the monkey.

The effect of chronic ethanol feeding on hepatic mitochondrial morphology and histochemically measured succinic dehydrogenase activity was assessed. Five monkeys of the species Macaca radiata received a nutritionally adequate diet containing 50% of the calories as ethanol, while five others were pair-fed the same diet except that ethanol was isocalorically substituted by carbohydrate. Liver morphology was assessed at 12 and 24 months and at sacrifice after 40 to 48 months of ethanol feeding. The ethanol-fed animals developed mild to moderate fatty liver as did some of the controls. No necrosis or fibrosis developed. All ethanol-fed animals developed centrilobolar megamitochondria and centrilobular "shift" in histochemically assayed succinic dehydrogenase activity characteristic of animals fed ethanol for prolonged periods. These mitochondrial changes persisted throughout the 48-month test period without progressive increase in severity or accompanying pathology. It is concluded that the morphologic and histochemically assessed mitochondrial changes do not necessarily represent a progressive destructive effect of ethanol.

Animals↗

PubMedDate not supplied

Effect of chronic ethanol feeding on hepatic collagen in the monkey.

The effect of chronic ethanol feeding was determined on parameters of hepatic collagen metabolism in the monkey. Four monkeys of the species Macaca radiata received a nutritionally adequate diet containing 50% of the calories as ethanol, while four others were pair-fed a diet in which ethanol was isocalorically substituted by carbohydrate. Liver biopsies were obtained at 3, 12, and 24 months, and the animals were killed between 40 and 48 months after initiation of the diets. The ethanol-fed animals developed various degrees of fatty infiltration, but no necrosis, inflammation, or fibrosis. The amount and distribution of collagen Types I, III, and IV demonstrated by immunohistochemical techniques was not altered after ethanol feeding. No changes were found in hepatic protein-bound hydroxyproline or in collagen prolyl hydroxylase activity at the various time intervals. Liver free proline and the incorporation of labeled proline into protein-bound hydroxyproline by liver slices were not altered after 40 to 48 months of ethanol feeding. This study shows that prolonged feeding of ethanol together with an adequate diet results in fatty infiltration but not deposition or alteration of hepatic collagen metabolism.

Animals↗

PubMedDate not supplied

Effect of parenteral amino acid supplementation in alcoholic hepatitis.

A controlled randomized study was performed in 15 patients with biopsy-proven alcoholic hepatitis to determine the effect of the administration of a parenteral amino acid-glucose solution for 1 month on nutritional, clinical, biochemical and histological parameters. All patients were allowed ad libitum consumption of a hospital diet. Five patients received the amino acid-glucose solution, while 10 received the glucose solution without amino acids. There was more improvement in nitrogen balance in the treated group than the control group. However, amino acid therapy was no more beneficial than control therapy in improving creatinine-height index, arm muscle area, arm fat area, and plasma levels of retinol binding proteins, prealbumin and pyridoxal-5'-phosphate. Clinical and biochemical markers of liver disease improved in both groups. This improvement in composite clinical index was more rapid in the treated than in the control group, but this early advantage was no longer apparent at the end of one month. Hepatocellular necrosis, inflammation and fat improved in the entire group. Amino acid treatment resulted in a greater resolution of fatty infiltration, but did not otherwise affect hepatic histology. Hepatocellular necrosis and inflammation in both the initial and final liver biopsies were highly correlated with nitrogen balance on admission. Initial clinical index correlated with the quantity of ethanol consumption prior to admission but not with liver injury on biopsy. However, by the end of the study, clinical index correlated with hepatocellular necrosis and inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Ethanol and H2-receptor antagonists.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Effect of growth hormone on alcohol dehydrogenase activity in hepatocyte culture.

The effect of growth hormone on the activity of alcohol dehydrogenase was determined in hepatocyte culture from normal and hypophysectomized male rats. Alcohol dehydrogenase activity was highest in hepatocytes harvested from hypophysectomized rats. The enzyme activity remained stable in hepatocytes harvested from normal rats during 2 to 6 days of culture but declined steadily in hepatocytes cultured from hypophysectomized rats. The combination of growth hormone (1 microgram per ml) and corticosterone (1 microM) increased alcohol dehydrogenase activity in hepatocytes from normal rats, while neither hormone alone had an effect. Corticosterone (1 microM) prevented the decline of the enzyme activity in hepatocytes from hypophysectomized rats, and the combination of growth hormone (1 microgram per ml) and corticosterone (1 microM) resulted in a further increase in enzyme activity. The increases in alcohol dehydrogenase, due to the exposure of the hepatocytes to the combination of growth hormone and corticosterone, were associated with increases in the rate of ethanol elimination. These observations indicate that growth hormone enhances liver alcohol dehydrogenase activity and ethanol elimination, and that this effect is dependent on the permissive influence of corticosterone.

Alcohol Dehydrogenase↗

PubMedDate not supplied

Ethanol and amino acid uptake by hepatocytes.

Explore the source record for details and available documents.

Amino Acids↗

PubMedDate not supplied

Lobular distribution of alcohol dehydrogenase in the rat liver.

The hepatic lobular localization of alcohol dehydrogenase was determined in male, female and castrated male rats. Alcohol dehydrogenase immunoreactive protein and activity were increased in female and castrated rats as compared to normal male rats. By immunohistochemistry, alcohol dehydrogenase protein was found localized principally in the perivenous area of the hepatic lobule in all of the animals. Alcohol dehydrogenase activity eluted from the male rat liver, during bidirectional digitonin perfusion, exhibited a pattern characteristic of cytosolic enzymes predominantly localized to the perivenous area. The elution of the enzyme was more rapid during cava-porta than porta-cava perfusion occurring in close association with the elution of glucokinase, an enzyme localized principally in the perivenous area. By contrast, elution of lactate dehydrogenase, which is located predominantly in the periportal area, preceded elution of alcohol dehydrogenase during porta-cava perfusion, but followed it during cava-porta perfusion. These differences were less apparent in the cava-porta than in the porta-cava direction. The predominant localization of alcohol dehydrogenase immunoreactive protein and activity to the perivenous area of hepatic lobule was not affected by sexual difference or increase in the enzyme following castration.

Alcohol Dehydrogenase↗