Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol and other alcohols stimulate adenylate cyclase activity in various tissues and potentiate its stimulation by some hormones. This effect, however, usually requires a high alcohol concentration. In some cases, an unknown substance, different from cyclic AMP, was formed from ATP in the presence of an alcohol and mimicked stimulation of adenylate cyclase. Ethanol inhibits phosphodiesterase activity in some tissues. In the brain, only the low affinity enzyme of pons-medulla region is inhibited. ATP levels and ATPase activities are affected by ethanol treatment and this can lead to secondary changes of the cyclic AMP levels. Cyclic AMP levels in the brain and liver are decreased by acute ethanol administration while levels in other organs are unchanged. High doses of ethanol inhibit the postdecapitation-induced rise of cyclic AMP level in the brain while low ethanol doses potentiate the postdecapitation rise of cyclic AMP in the lower brain stem. Chronic ethanol administration increases basal adenylate cyclase activity and cyclic AMP levels, and decreases stimulation of adenylate cyclase by norepinephrine in the brain. In contrast, the stimulation of cyclic AMP formation by norepinephrine and other biogenic amines is increased in the brain of ethanol-withdrawn animals. Chronic administration of ethanol affects also cyclic AMP levels and cyclic AMP formation in some peripheral organs. Cyclic AMP might be involved in ethanol-induced fatty liver, since it activates hepatic lipase and might also participate in the fatty acid oxidation.
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PMID:Interactions of ethanol with cyclic AMP. 16 56

1. The effect of ethanol on the metabolism of [1-(14)C]palmitate in rat liver was investigated in a single-pass perfusion system at concentrations of 10mm- or 80mm-ethanol and 0.2mm- or 1mm-palmitate. 2. After the perfusion the hepatic lipid was isolated in subcellular fractions. The two major fractions contained triacylglycerol from cytoplasmic lipid droplets and from endoplasmic reticulum plus Golgi apparatus respectively. 3. In experiments with 0.2mm-palmitate perfusion with 10mm- or 80mm-ethanol did not measurably increase the esterification, and the oxidation was markedly decreased and the fatty acid uptake was not affected. 4. Perfusion with ethanol, at 1mm-palmitate, increased the fatty acid uptake, increased esterification and decreased oxidation. The effects of 10mm- and 80mm-ethanol were similar. The incorporation of [1-(14)C]palmitate into triacylglycerol in cytoplasmic lipid droplets was not affected statistically significantly by ethanol. Ethanol increased the incorporation of [1-(14)C]palmitate into di- and tri-acylglycerol in the membranous fraction. Estimated chemically, the contents of di- and tri-acylglycerol were only slightly affected by ethanol. These results suggest that the effect of ethanol was to increase the turnover of fatty acids in triacylglycerol rather than to increase its accumulation. 5. The results indicate that an increased concentration of fatty acids is more important for the formation of acute fatty liver in fed rats than are the direct effects of ethanol on hepatic fatty acid metabolism.
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PMID:Metabolism of palmitate in perfused rat liver. Effect of low and high ethanol concentrations at various concentrations of palmitate in the perfusion medium. 53 22

The effect of chronic ethanol feeding on the status of alpha- and gamma-tocopherol in plasma, liver, lung, and testes of Sprague-Dawley rats was characterized. Rats were pair-fed liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates. After 3 weeks, ethanol ingestion resulted in a significant (p less than or equal to 0.05) increase in liver weight and induced fatty liver without affecting total body weight. Ethanol feeding did not affect the plasma concentration of alpha-tocopherol but doubled that of gamma-tocopherol. When expressed per milligram of tissue, liver alpha-tocopherol did not vary with ethanol ingestion, whereas gamma-tocopherol concentration increased 2.5 times that of control animals. However, the concentration of alpha-tocopherol expressed per milligram of total lipids was significantly (p less than or equal to 0.01) decreased in the liver with ethanol feeding. In contrast to the liver, ethanol feeding significantly increased alpha- and gamma-tocopherol levels per milligram of total lipids in the testes. The concentration of gamma-tocopherol (but not alpha-tocopherol) per milligram of lung tissue and per total lung was significantly (p less than or equal to 0.05) increased with ethanol feeding. These data indicate that chronic ethanol ingestion significantly alters the distribution of alpha-tocopherol and gamma-tocopherol in hepatic and extrahepatic tissues of the rat.
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PMID:Effect of chronic ethanol feeding on hepatic and extrahepatic distribution of vitamin E in rats. 175 7

In this study special care was taken to discriminate between the direct effect of ethanol on hepatocarcinogenesis and secondary effects such as choline deficiency or fatty liver. Rats were divided into 2 groups, D and N. Group D was initiated using 3'-Me-DAB, while the control group N was not initiated. Groups N and D were divided into 4 sub-groups. Each subgroup was given, in the drinking water, one of the following ethanol solutions: 0, 5, 10 or 15% for 45 weeks. Liver tumors were induced only in D groups. Evidence obtained indicates that: (a) in the N group, ethanol did not cause any apparent disorders in histology and lipid metabolism, and (b) in the D group no significant differences were observed in the incidence of HCCs and other liver lesions. Ethanol thus does not appear to enhance hepatocarcinogenesis, at least in the absence of liver injury.
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PMID:Effect of ethanol on hepatocarcinogenesis initiated in rats with 3'-methyl-4-dimethylaminoazobenzene in the absence of liver injuries. 250 54

The (+)-cyanidanol-3 is used as an antihepatotoxic and hepatoprotective drug in both men and animals against alcoholic and experimental liver injury. Histologic staining techniques give mostly qualitative or semiquantitative description of liver damages. Experiments have been carried out to determine the hepatoprotective effects of (+)-cyanidanol-3 on alcoholic liver damage (i.e., fatty liver and hepatomegaly) by morphometric measurement of the liver tissue sections. Ethanol was administered ad lib to CFY rats to cause mild alcoholic liver damage together with 200 mg/kg/day (+)-cyanidanol-3 to prevent the tissue deterioration. The changes of hepatic lobule and hepatocytes were measured morphometrically. The chronic ethanol consumption results in hepatocellular hypertrophy, a significant increase in size of the hepatocytes and a mild increase of the intralobular extrahepatocytic space as well when compared with controls. The volume of cytoplasm was increased while the parameters of nuclei were unchanged. The (+)-cyanidanol-3 prevents changes and the morphometric parameters in the treated group were almost the same as in the controls. The treatment with (+)-cyanidanol-3 alone does not affect the hepatic tissue parameters. The results show the hepatoprotective effect of (+)-cyanidanol-3 and the suitability of the morphometric method for quantitative comparison of normal and experimentally-altered liver cells.
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PMID:Some morphometric evidence of hepatoprotective effects of (+)-cyanidanol-3. 258 92

The supply of ethanol and other substances to the rat has necessitated the development of quite complex dietary preparation and feeding techniques. This study reports the use of ethanol/water solutions in conjunction with normal rat chow diet to provide up to 30 g/kg/day ethanol to study animals. By additionally supplying agar gels containing ethanol, voluntary intake of ethanol was raised to a possible maximum of 48 g/kg/day. Hepatic steatosis was produced in 7/18 rats supplied ethanol in this fashion. Agar gels were also used to provide carbonyl iron to rats and it produced grade 3 to 4 hepatocyte iron loading in all study animals. The study demonstrates a practical method for administering ethanol and iron to rats without altering normal dietary intake. Ethanol supplied in this way does produce hepatic injury in the rat.
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PMID:A histological study of the use of agar as a delivery vehicle for alcohol or iron to rats. 271 91

The effects of ethanol administration on activity and regulation of carnitine palmitoyltransferase I (CPT-I) were studied in hepatocytes isolated from rats fed a liquid, high-fat diet containing 36% of total calories as ethanol or an isocaloric amount of sucrose. Cells were isolated at several time points in the course of a 5-week experimental period. Ethanol consumption markedly decreased CPT-I activity and increased enzyme sensitivity to inhibition by exogenously added malonyl-CoA. Changes in enzyme activity occurred sooner than those in enzyme sensitivity. Fatty acid oxidation to CO2 and ketone bodies was depressed in hepatocytes from ethanol-fed animals during the first part of the treatment. At the end of the 35-day period, there were no longer differences in the rate of ketogenesis between the two groups. At that time, however, the rate of CO2 formation was still impaired in the ethanol-fed animals. Furthermore, addition of ethanol or acetaldehyde to the incubation medium strongly depressed CPT-I activity and rates of fatty acid oxidation in hepatocytes from ethanol-treated rats, whereas these effects were much less pronounced in cells from control animals. The response of CPT-I activity to insulin, glucagon, vasopressin, and phorbol ester was blunted in cells derived from ethanol-fed rats. These changes in the regulation of CPT-I activity corresponded with those observed in the rate of fatty acid oxidation. It is concluded that CPT-I may play a role in the generation of the ethanol-induced fatty liver.
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PMID:Effects of ethanol feeding on the activity and regulation of hepatic carnitine palmitoyltransferase I. 306 12

The metabolic effects of ethanol are due to a direct action of ethanol or its metabolites, changes in the redox state occurring during its metabolism, and modifications of the effects of ethanol by several nutritional factors. Ethanol causes hyperglycemia or hypoglycemia depending whether or not glycogen stores are adequate, inhibits protein synthesis, and results in a fatty liver and elevations in serum triglyceride levels. Increases in serum lactate, results from the increased reduced nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide + (NADH/NAD+) ratio, and hyperuricemia probably occurs owing to the increased turnover of adenine nucleotides after ethanol ingestion. Ethanol decreases thiamine absorption and decreases the enterohepatic circulation of folate. Acetaldehyde, the major metabolite of ethanol, increases the degradation of pyridoxal 5'-phosphate by displacing it from its binding protein and making it susceptible to hydrolysis by membrane-bound alkaline phosphatase. Chronic ethanol administration also results in decreased vitamin A stores and reduced bone mass and blood levels of 25-hydroxyvitamin D. The mechanism whereby ethanol affects these vitamins and their associated enzymes is unknown.
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PMID:The effect of ethanol and its metabolites on carbohydrate, protein, and lipid metabolism. 329 39

Severe hepatic steatosis and focal necrosis of hepatocytes have previously been induced in rats by continuous intragastric infusion of ethanol and a diet containing only 5% fat as a per cent of total calories as reported by us previously. Since the ethanol diet fed ad libitum with such a low level of fat has previously failed to produce alcoholic fatty liver, continuously high blood alcohol levels achieved in this model appeared to be key in induction of the progressive pathologic lesions in the liver. In the current study, effects of increased fat intake on alcohol-induced liver injury were investigated. Seventeen pairs of male Wistar rats were implanted with gastrostomy cannulas and infused with a liquid diet containing 25% of total calories as fat plus ethanol or isocaloric dextrose. Ethanol intake was progressively increased from 32% up to 47% of total calories to maintain sustained intoxication for 30 to 120 days. Light and electron microscopic examination of the liver revealed moderate to severe fatty infiltration in all of the ethanol-fed rats, of which 14 had spotty or zonal necrosis in the centrilobular areas accompanied by polymorphonuclear and mononuclear cell infiltration. In addition, fibrosis was observed in association with the necrotic lesions or with large-droplet steatosis. Reticulin and trichrome stains clearly demonstrated fine fibrosis, including perivenular fibrosis as well as septum formation progressing to bridging fibrosis. Furthermore, increased numbers of Ito cells and myofibroblasts were observed in the perivenular fibrotic areas. These results demonstrate striking potentiation of alcohol-induced liver injury by the increased fat intake or by the concomitant decrease in carbohydrate intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol-induced liver fibrosis in rats fed high fat diet. 375 35

The metabolic effects of ethanol are due to a direct action of ethanol or its metabolites, changes in the redox state occurring during its metabolism, and modifications of the effects of ethanol by nutritional factors. Ethanol causes hyperglycemia or hypoglycemia depending on whether glycogen stores are adequate, inhibits protein synthesis, and results in fatty liver and in elevations in serum triglyceride levels. Increases in high-density lipoprotein cholesterol after ethanol ingestion may explain the lower risk of myocardial infarction and death from coronary disease after moderate drinking. Increases in serum lactate, resulting from the increased NADH/NAD+ ratio, and hyperuricemia, most likely the result of increased turnover of adenine nucleotides, are common transient effects of ethanol ingestion. Causes of vitamin deficiencies in alcoholism are decreased dietary intake, decreased intestinal absorption, and alterations in vitamin metabolism. Ethanol decreases thiamine absorption and decreases the enterohepatic circulation of folate. Acetaldehyde increases the degradation of pyridoxal 5'-phosphate by displacing it from its binding protein and making it susceptible to hydrolysis by membrane-bound alkaline phosphatase. Ethanol decreases hepatic vitamin A concentration and its conversion to active retinal, and modifies renal metabolism of vitamin D.
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PMID:Metabolic effects of alcohol. 388 Dec 85


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