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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of ethanol plus fat diet has been investigated in our laboratory in relation to the experimental fatty liver in rats. Considering that lipid metabolism are markedly altered in these experimental conditions, the present work studies the effect of simultaneous administration of Coenzyme A (CoA) on the alterations produced by ethanol and lipid diet on glycolytic and lipogenic routes. Ethanol was administered in a 15% solution as the only drinking fluid and a high fat diet (45% vegetable fat as total calories) for three months. CoA was intraperitoneally administered at a dose level of 1.0 mg/Kg body weight/day. Enzymatic activities were determined in the soluble fraction of liver homogenates. The methods used for the estimation of the enzymatic activities are described by Bergmeyer. The most significant changes found by the effect of CoA administration correspond to malic enzyme, citrate lyase and 6-phosphogluconate dehydrogenase. Fatty acid synthetase and glycolytic kinases, especially diminished by the effect of fat diet, did not show any significant restoration of their activities when ethanol and CoA were simultaneously administered.
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PMID:Metabolic repercussion of coenzyme-A (CoA) in experimental ethanol hepatopathy. 712 69

To clarify contributions of alcoholic liver injury, dietary fat and acute ethanol intake to alcoholic hypertriglyceridemia, control subjects and alcoholics with fatty liver or cirrhosis were given a high fat meal with and without ethanol. The triglyceridemic response to the meal in patients with fatty liver (551.3 +/- 98.4 mg x hr/dl) was enhanced compared to controls (106.4 +/- 30.9) and characterized by increased fasting and postprandial pre-beta lipoproteins. The cirrhotics' response (262.5 +/- 34.9) was characterized by minimal fasting and postprandial pre-beta lipoproteins and increased postmeal chylomicrons. Ethanol added to the meal enhanced the lipemic response of controls, barely altered the response of patients with fatty liver, and decreased the response of cirrhotics. In an expanded group of alcoholic patients, the percentage of pre-beta lipoproteins determined by electrophoresis reflected the degree of liver injury. Therefore, major determinants of alcoholic triglyceridemia are stage of liver injury and dietary lipid; electrophoretic determination of pre-beta lipoproteins may indicate degree of alcoholic liver damage.
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PMID:Relationship of alcoholic hypertriglyceridemia to stage of liver disease and dietary lipid. 735 47

Ethanol-induced fatty liver in rats was attenuated by repeated running exercise, and the protective effect of exercise was associated with the synergistic expression of heat shock proteins (HSP72). Rats were placed in four groups of six. The two ethanol-fed groups of rats received a liquid diet (Lieber-DeCarli formulation) in which 36% of the calories were derived from ethanol. One group remained sedentary (S/E), whereas the other was trained to run on a rodent treadmill at a speed of 27 m/min, 1 hr/day, 5 days/week, for 7 weeks (R/E). Two other groups--one exercised as previously mentioned (R/C) and one sedentary (S/C)--received control-liquid diets in which the ethanol was isocalorically substituted with a dextran/maltose mixture. The degree of fatty infiltration in liver sections stained with hematoxylin and eosin was graded on a 0-4 scale and the data analyzed by ANOVA on ranks. Ethanol significantly induced fatty infiltration in the S/E group, whereas fatty infiltration in the livers of the R/E group was not different from the S/C group. Electrophoresis and Western blotting of liver homogenates demonstrated that HSP72 was not expressed in either the S/C or S/E groups and was only slightly expressed in the R/C group. The combination of exercise and ethanol, however, resulted in an elevated expression of HSP72 in the R/E group. The content of HSP73 was unaffected by any treatment.
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PMID:Induction of HSP72 in rat liver by chronic ethanol consumption combined with exercise: association with the prevention of ethanol-induced fatty liver by exercise. 757 4

Carnitine-mediated prevention of ethanol-induced hepatic steatosis is related to the attenuation of ethanol metabolism by carnitine in the intact rat. Although carnitine retards ethanol oxidation in the intact animal, the in vitro activities of ethanol-metabolizing enzymes remain unaltered. Therefore, hepatocytes were targeted to understand the mechanism of carnitine effect on ethanol metabolism. Rat hepatocytes were isolated by a collagenase-perfusion technique and incubated in albumin-containing medium with ethanol in the presence or absence of added carnitine or related compounds. Ethanol oxidation was determined by the loss of ethanol as well as by the products formed. The rate of ethanol oxidation in the presence of carnitine was one-half the rate in the absence of carnitine (14 vs. 25 nmol.min-1.million-1 cells). It took 100 times the concentration of carnitine to equal the maximal inhibition produced by acetylcarnitine and the effect of acetylcarnitine was without a lag time. It is concluded that acetylcarnitine is the mediator of carnitine inhibition of ethanol oxidation.
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PMID:Acetylcarnitine-mediated inhibition of ethanol oxidation in hepatocytes. 763 64

Deficiency of choline and methionine produces hepatic steatosis similar to that seen with ethanol, and supplementation with these lipotropes can prevent ethanol-induced fatty liver. These effects are thought to occur through alterations in membrane phospholipid metabolism, but the mechanism whereby this occurs and the precise nature of the changes brought about by ethanol in the interactions of choline and methionine metabolism remain unclear. Through the known effects on hepatic glutathione (which requires as a precursor a product of methionine catabolism), ethanol might affect hepatic one-carbon metabolism, which requires the participation of both methionine and choline in the transfer of methyl groups. This has been investigated with a radiorespirometric technique to assess the in vivo oxidation of the methyl groups of lipotropes and their intermediates in ethnaol- and control-fed rats. Enzyme activities of one-carbon transfer reactions and the hepatic levels of methionine and alpha-aminobutyrate, an end product of methionine catabolism, have been measured. The effect of ethanol feeding on hepatic S-adenosylmethionine and S-adenosylhomocysteine has also been assessed. Ethanol increases the oxidation to carbon dioxide of the methyl group of methionine by a factor of 2.9 (p = 0.002) and produces a 3.6-fold (p = 0.0001) accumulation of alpha-aminobutyrate, indicating a marked increase in methionine catabolism. Hepatic methionine levels are unchanged by ethanol, however, and this may be explained by a dramatic increase in the turnover of the methyl groups of choline and betaine in response to ethanol (times 3.6 and 4.2, respectively, p < 0.003), suggesting greatly increased use of the choline oxidation pathway to remethylate homocysteine through betaine homocysteine methyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage. 769 9

Free radical products have previously been detected in rodents after chronic feeding with an ethanol-containing, high-fat diet. The significance of reactive free radical formation in ethanol-induced hepatotoxicity has been difficult to assess because most rodent models exhibit only fatty liver. However, serious hepatic damage resembling clinical alcoholic liver injury (e.g., steatosis, inflammation, and necrosis) occurs in rats after continuous intragastric administration of an ethanol-containing, high-fat diet developed by Tsukamoto and French. Accordingly, rats treated with ethanol for at least 2 weeks using this protocol were administered the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, and bile samples were collected. A six-line radical adduct spectrum was detected in the bile of ethanol-treated rats. A similar spectrum of lower intensity was detected with rats fed a high-fat diet without ethanol, but little or no radical adduct signal was detected with chow-fed animals. For both treatment groups, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone and extra ethanol were given acutely. Destruction of Kupffer cells by chronic treatment with GdCl3 decreased by about 50% the radical adduct formation in rats fed the ethanol-containing, high-fat diet. This radical species was largely ethanol derived, because addition of [13C]ethanol produced a 12-line spectrum, indicating the formation of alpha-hydroxyethyl radical. Ethanol treatment also caused hypoxia (detected on the liver surface in vivo with oxygen electrodes), which was reflected in a dose-dependent decrease in oxygen tension with ethanol. The effect was blocked by GdCl3. Hepatic damage detected by histology was prevalent in ethanol-treated rats but only mild fatty liver was observed in high-fat diet-fed controls. GdCl3 treatment eliminated hepatic damage due to high-fat and ethanol diets, and when all groups were compared a significant correlation between liver injury and radical adduct signal was observed. Thus, free radical formation in ethanol-treated rats has been detected for the first time in a model that exhibits injury characteristic of human alcoholic injury, and signal intensity correlates with hepatotoxicity. Moreover, the decrease in both free radical formation and hepatic damage produced by GdCl3 implicates Kupffer cells in the development of alcoholic liver injury. This important pathophysiological process may involve direct production of reactive oxygen species or indirect actions of mediators on parenchymal cells.
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PMID:Free radical adducts in the bile of rats treated chronically with intragastric alcohol: inhibition by destruction of Kupffer cells. 774 69

Following the pioneer report of Di Luzio (Physiologist 6, 169-173, 1963) concerning the prevention of the acute ethanol-induced fatty liver by antioxidants, many observations have shown that ethanol-induced liver injury may be linked, at least partly, to an oxidative stress resulting from increased free radical production and/or decreased antioxidant defence. The disturbances induced in the major hepatic enzymatic and non-enzymatic antioxidant systems following experimental acute and chronic ethanol administration are reviewed, emphasizing the important role of dietary alpha-tocopherol in modifying the induction of oxidative stress and its usual expression as increased lipid peroxidation. Adaptative increases in some elements of the hepatic antioxidant defence partly counteract the enhanced generation of prooxidant free radicals following chronic ethanol intake. By contrast, lipid peroxidation is favoured when ethanol is administered together with a fat-rich diet and/or various xenobiotics. Chronic ethanol feeding has also been reported to potentiate the oxidative stress resulting from an acute ethanol load. By generating potent chemoattractants for human neutrophils and/or by stimulating the expression of genes involved in collagen biosynthesis, liver lipid peroxidation may play an important role in the progression of steatosis to hepatitis and cirrhosis. Oxidative stress has been shown not to be restricted to the liver, but also to affect, under some experimental conditions of ethanol administration, extrahepatic tissues, such as the central nervous system, the heart and the testes. This stress can be partly prevented by vitamin E supplementation. Ethanol-induced antioxidant disturbances have also been reported in clinical studies in blood and liver biopsies. Pharmacological antioxidants could have beneficial effects in reducing the incidence of ethanol-induced changes in cellular lipids, proteins and nucleic acids. The antioxidants considered could act by reducing free radical production (e.g. chelators of redox-active iron derivatives), trapping free radicals themselves, interrupting the peroxidation process or reinforcing the natural antioxidant defence.
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PMID:Alcohol and antioxidant systems. 781 35

Liver lipid peroxidation, nonheme iron, antioxidants, and protein oxidation were investigated in experimental alcohol-induced liver disease in the rat. Wistar male rats were intragastrically and continuously infused for 4 weeks with a high-fat diet plus an ethanol or an isocaloric amount of dextrose, maintaining a high blood alcohol level (200-300 mg%). This model induced fatty liver, spotty necrosis, and focal inflammation. This pathology was associated with an enhanced lipid peroxidation and a decrease in the major antioxidant factors. Hepatic alpha-tocopherol and glutathione concentrations were significantly decreased in ethanol-fed rats. Glutathione peroxidase (GPx) was also decreased, whereas glutathione S-transferase (GST) was unaffected. The nonheme iron level was significantly decreased. Protein oxidation was assessed through three parameters: protein thiols, protein carbonyl groups, and the activity of glutamine synthetase (GS), a centrilobular enzyme particularly susceptible to free-radical-mediated damage. Ethanol-fed rats had decreased protein thiol concentrations and reduced GS activity, together with increased protein carbonyls. A significant correlation between GS activity and the pathological score was observed. This study confirms the ethanol-related increase in lipid peroxidation and shows that ethanol impairs the hepatic antioxidant potential. Furthermore, evidence of oxidative protein damage is given, including decreased activity of a key enzyme of ammonia metabolism. These protein disturbances may contribute to the pathogenesis of the observed liver damage.
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PMID:Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. 902 46

We studied the effect of the long-acting parenteral iron chelator, hydroxyethyl starch deferoxamine (HES-DFO) on liver nonheme iron, lipid peroxidation and pathologic changes in the liver in the intragastric feeding rat model for alcoholic liver disease. Male Wistar rats (225-250 g) were fed liquid diet and ethanol for 2 months. In control pair-fed animals, ethanol was isocalorically replaced by dextrose. Two additional groups of animals (dextrose and ethanol fed) received HES-DFO (25 mg deferoxamine equivalents/kg, three times a week). The blood ethanol level in the ethanol-fed animals was maintained between 150 and 350 mg/dl. For each animal, the levels of hepatic nonheme iron, lipid peroxidation and pathologic changes were evaluated. Ethanol administration caused fatty liver, necrosis and inflammation. Addition of HES-DFO to the ethanol diet increased the severity of pathologic changes, particularly necrosis and inflammation. The nonheme iron in alcohol-fed animals was significantly higher (18.3 +/- 4.3 microg liver) than in pair-fed dextrose controls (12.5 +/- 1.5 microg, P < .05). Addition of HES-DFO significantly increased nonheme iron levels in the dextrose-fed rats (17.1 +/- 2.0 microg/g, P < .02) but not in ethanol-fed rats (20.0 +/- 2.0). Ethanol increased levels of conjugated dienes; these levels were not altered by HES-DFO. The most significant observations in this study were: 1) the higher hepatic nonheme iron content in ethanol-fed rats compared with pair-fed dextrose controls; 2) the absence of changes in hepatic nonheme iron levels or lipid peroxidation in ethanol-fed groups treated with HES-DFO; and 3) the worsening of liver injury in ethanol-fed rats by HES-DFO.
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PMID:The long-acting parenteral iron chelator, hydroxyethyl starch-deferoxamine, fails to protect against alcohol-induced liver injury in rats. 902 21

Acute treatment with one large dose of ethanol, which mimics binge drinking, causes marginal fatty liver and decreases survival significantly after liver transplantation in rats, yet mechanisms remain unclear. Therefore, we evaluated the possible role of free radicals in primary nonfunction caused by acute ethanol. Female donor rats were administered ethanol (5 g/kg orally) 20 hr before explantation, and grafts were stored in UW cold storage solution for 24-42 hr before implantation. Free radicals were trapped with alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone after transplantation, and adducts were detected using electron spin resonance spectrometry. Ethanol increased a carbon-centered radical adduct in bile approximately 2-fold and elevated serum lipid hydroperoxides approximately 4-fold. Ethanol also increased transaminase release 3.7-fold and decreased bile production by 55%. Catechin, a free radical scavenger, minimized the increase in free radicals, blunted transaminase release, and elevated bile production significantly, indicating that free radical production plays an important role in ethanol-induced fatty graft injury. GdCl3 (20 mg/kg intravenously), a selective Kupffer cell toxicant, largely blocked the increases in free radical and lipid hydroperoxide production caused by ethanol. In addition, ethanol nearly doubled white blood cell adhesion after transplantation, leading to increased superoxide production in fatty grafts. GdCl3 largely blocked leukocyte adhesion as well as superoxide production. Allopurinol, an inhibitor of xanthine oxidase, also diminished free radical production, blunted transaminase release, and improved bile production in fatty grafts significantly. Taken together, we conclude that free radical formation increases in ethanol-induced fatty grafts due mainly to activation of Kupffer cells and increased adhesion of white blood cells. Antioxidants can effectively block free radical formation and minimize injury to marginal fatty grafts caused by binge drinking.
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PMID:Role of free radicals in primary nonfunction of marginal fatty grafts from rats treated acutely with ethanol. 935 83


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