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

Alcoholism is a major health problem, and one of its primary manifestations is alcoholic liver disease. The mechanisms responsible for the various forms of alcoholic liver disease--fatty liver, alcoholic hepatitis, and cirrhosis--are at present poorly understood. Knowledge of these mechanisms is needed to provide a sound framework for the therapy and prevention of liver disease due to alcohol and for the identification of those individuals most susceptible to develop liver disease from alcohol abuse. These experiments were designed specifically to evaluate the postulate that ethanol-induced pericentral liver damage results from an accentuated gradient of decreasing oxygen tension leading to pericentral hypoxia. Microlight guides were used to detect NADH fluorescence, and miniature oxygen electrodes were employed to measure oxygen tensions from periportal and pericentral regions of the liver lobule from the perfused rat liver. With both techniques, ethanol treatment increased the hepatic oxygen gradient. This increase was blocked by the antithyroid drug propylthiouracil. Thus, these experiments provide evidence in support of the hypothesis that pericentral hypoxia is involved in the mechanism of ethanol-induced liver injury. Furthermore, low-flow hypoxia was shown to cause blebs in the pericentral region of the liver lobule in as little as 15 min. This surface blebbing could represent the mechanism for the well-known release of enzymes by impaired hepatic tissues.
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PMID:Alcohol-induced liver injury. The role of oxygen. 637 78

Since alcoholism is a major health problem, mechanisms responsible for various forms of alcoholic liver disease (e.g., fatty liver, alcoholic hepatitis, and cirrhosis) require elucidation. Knowledge of these mechanisms is needed to provide a sound framework to treat alcoholic liver disease, to prevent its occurrence and to identify those most susceptible to it. Israel and co-workers proposed that ethanol-induced necrosis results from hypoxia to centrilobular hepatocytes as a consequence of an alcohol-induced increase in hepatic oxygen utilization (Y. Israel, H. Kalant , H. Orrego , J. M. Khanna , L. Videla , and J. M. Phillips, 1975, Proc. Natl. Acad. Sci. USA, 72(3), 1137-1141). We have employed several new techniques to evaluate this hypothesis. Procedures have been developed to make measurements of hepatic metabolism within the hepatic lobule in the isolated, perfused liver using miniature light guides and oxygen electrodes. By comparing these lobular measurements to global metabolism and to hepatic morphology determined by light and electron microscopy, a coherent, quantitative description of lobular oxygen metabolism is emerging. With these techniques, the lobular oxygen gradient was measured directly in isolated, perfused rat livers. This gradient was elevated in livers from ethanol-treated rats, an effect which was blocked by the antithyroid drug, propylthiouracil. Restriction of oxygen delivery to the isolated liver produced stable, circumscribed zones of virtual anoxia localized around the central vein. Anoxic stress led within minutes to centrilobular injury with complete sparing of periportal areas. Cellular injury was characterized by the formation of membranous blebs on the surface of centrilobular hepatocytes. When hypoxic tissue was reoxygenated , blebs were released into the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is hypoxia involved in the mechanism of alcohol-induced liver injury? 672 87

The conversion of xanthine dehydrogenase to xanthine oxidase that produces oxygen radicals has been implicated in the ischemic injury to the myocardium and to the kidney. Xanthine dehydrogenase uses NAD as the electron acceptor to catalyze a reaction which does not produce any oxygen free radicals and may depress the conversion of xanthine dehydrogenase to xanthine oxidase. Nicotinamide is the preferred precursor for NAD. This study was conducted to examine the effect of an 18% casein diet supplemented with 0.5% nicotinamide on the activity of oxidoreductase and its two enzyme forms, xanthine dehydrogenase and xanthine oxidase, in kidney, heart and liver of female obese Zucker rats that spontaneously develop glomerulosclerosis, cardiomegaly and fatty liver. Lean litter mates were used as controls. Nicotinamide supplementation had no effect on the activities of these enzyme forms in the liver of either obese rats or lean rats. Obese rats fed the nicotinamide supplemented diet had higher activities of these enzyme forms in kidneys and hearts than unsupplemented diet fed obese rats, but this difference was not observed in lean rats. In unsupplemented rats, xanthine oxidase activity in the kidney was greater in lean rats than obese rats. Thus, the abnormalities observed in obese rats are unlikely attributable to the xanthine oxidase-mediated oxidant stress.
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PMID:Dietary nicotinamide supplementation increases xanthine oxidoreductase activity in the kidney and heart but not liver of obese Zucker rats. 761 99

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

The study investigates the effect of a singular dose of CCl4 (2.5 ml/kg) on the concentration of triacylglycerols in the liver and oxidative phosphorylation in hepatic mitochondria after 24, 72 hours, 2 and 4 weeks since CCl4 application. It was discovered that 24 and 72 hours after CCl4 application the concentration of triacylglycerols increased significantly and steatosis of the liver supervened. After 2 and 4 weeks the triacylglycerol concentration values reached the level of those of control. The hepatic steatosis disappeared. The indices of oxidative phosphorylation index of respiration control, oxygen consumption during stimulated respiration (state 3), oxygen consumption during basal respiration (state 4), and phosphorylation velocity decreased significantly after 24 and 72 hours after CCl4 application in all observed substrates--glutamate, pyruvate and jantarane. After 2 to 4 weeks the observed indices reached the level of values characteristic for healthy controls. The results have indicated that after the CCl4 toxic impairment the energy metabolism in hepatic mitochondria has been significantly impaired. This impairment, in spite of its severeness, was irreversible and hepatocytes were able to compensate it (Tab. 4, Ref. 33).
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PMID:[Oxidative phosphorylation in liver mitochondria after injury with carbon tetrachloride and during regeneration]. 781 46

Effects of acetylsalicylic acid (ASA) (aspirin) on the pathogenesis of fatty liver, cirrhosis and hepatocarcinogenesis caused by a choline-deficient L-amino acid-defined (CDAA) diet were examined in male Fischer 344 rats fed a CDAA diet supplemented with 0, 0.1, 0.2, 0.4 or 0.8% ASA for 30 weeks. ASA at concentrations of > 0.2% prevented the development of both cirrhosis and preneoplastic and neoplastic nodules, but without any directly associated prevention of fatty changes. ASA also prevented hepatocyte proliferation and the generation of thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine caused by feeding the CDAA diet, analyzed, respectively, after 1, 12 and 12 weeks. The results clearly indicate that the anti-inflammatory drug ASA, which is not a lipotropic factor, can prevent the pathogenesis of cirrhosis and hepatocarcinogenesis caused by a CDAA diet, which is possibly partly associated with the prevention of reactive oxygen species production.
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PMID:Prevention by acetylsalicylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino acid-defined diet in rats. 802 Jan 68

It is well recognized that consumption of alcohol leads to liver disease in a dose-dependent manner; however, the exact mechanisms remain unclear. Hypoxia subsequent to a hypermetabolic state may be involved; therefore, when it was observed recently that inactivation of Kupffer cells prevented stimulation of hepatic oxygen uptake by alcohol, the idea that Kupffer cells participate in early events that ultimately lead to alcohol-induced liver disease became a real possibility. The purpose of this study was to test that hypothesis. Male Wistar rats were exposed to ethanol continuously by means of intragastric feeding for up to 4 weeks using the model developed by Tsukamoto and French. In this model, ethanol causes fatty liver, necrosis and inflammation--changes characteristic of alcohol-induced liver disease in human beings. Kupffer cells were inactivated by twice weekly treatment with gadolinium chloride (GdCl3), a selective Kupffer cell toxicant. AST levels were elevated to 192 +/- 13 and 244 +/- 56 IU/L in rats exposed to ethanol for 2 and 4 wk, respectively (control value, 88 +/- 7). This injury was prevented almost completely by GdCl3 treatment. Fatty changes, inflammation and necrosis were also all reduced dramatically by GdCl3 treatment. The average hepatic pathological score of rats treated with ethanol for 4 wk was 4.3 +/- 0.6, which was reduced significantly in ethanol- and GdCl3-treated rats to 1.8 +/- 0.5 (p < 0.05). Rates of ethanol elimination were elevated 2- to 3-fold in rats exposed to ethanol for 2 to 4 wk. This elevation was blocked by GdCl3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inactivation of Kupffer cells prevents early alcohol-induced liver injury. 804 7

Oxidative stress in the course of diabetes mellitus can cause disturbance of lipid membranes of cellular organelles. The study is aimed at the determination of oxidative phosphorylation in mitochondria in rats with experimentally induced acute and chronic insulin-dependent diabetes mellitus (IDDM). IDDM was induced by single dose of streptozotocin (45 mg per kg-1). Insulin Interdep (6 U per kg-1) was administered once a day subcutaneously. The authors investigated glycaemia, cholesterol and triacylglycerol concentrations in the blood and liver. Isolation of mitochondria was succeeded by measurement of oxidative phosphorylation indicators after 8 days (acute IDDM) or after 8 weeks (chronic IDDM) from streptozotocin administration. The authors found out that both acute and chronic IDDM were concommited by hyperglycaemia. The group with acute IDDM yielded an increase in cholesterol and triacyglycerols concentrations in the blood, as well as that of cholesterol in the liver. The group with chronic IDDM yields an increase in cholesterol in the blood. Trialcylglycerols in the liver increased in none of the investigated groups. Liver steatosis did not occur. Indicators of oxidative phosphorylation in the liver mitochondria of rats with acute and with chronic IDDM decreased in contrast to healthy controls from NAD substrates glutamate and pyruvate and also form FAD substrate of succinate. Significant decrease in consumption of oxygen in the 3 state occurred, while in acute IDDM the decrease was more significant than in chronic IDDM. Phosphorylation rate significantly decreased in contrast to controls, but there was no difference between IDDM groups. The investigation results imply that in both acute and chronic IDDM there are decreased effectivity of energetic metabolism in liver mitochondria. (Tab. 5, Ref. 29.).
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PMID:[Bioenergetics of liver mitochondria in rats in experimental insulin-dependent diabetes]. 901 45

Alcohol-induced tissue damage results from associated nutritional deficiencies as well as some direct toxic effects, which have now been linked to the metabolism of ethanol. The main pathway involves liver alcohol dehydrogenase which catalyzes the oxidation of ethanol to acetaldehyde, with a shift to a more reduced state, and results in metabolic disturbances, such as hyperlactacidemia, acidosis, hyperglycemia, hyperuricemia and fatty liver. More severe toxic manifestations are produced by an accessory pathway, the microsomal ethanol oxidizing system involving an ethanol-inducible cytochrome P450 (2E1). After chronic ethanol consumption, there is a 4- to 10-fold induction of 2E1, associated not only with increased acetaldehyde generation but also with production of oxygen radicals that promote lipid peroxidation. Most importantly, 2E1 activates many xenobiotics to toxic metabolites. These include solvents commonly used in industry, anaesthetic agents, medications such as isoniazid, over the counter analgesics (acetaminophen), illicit drugs (cocaine), chemical carcinogens, and even vitamin A and its precursor beta-carotene. Furthermore, enhanced microsomal degradation of retinoids (together with increased hepatic mobilization) promotes their depletion and associated pathology. Induction of 2E1 also yields increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. New therapies include adenosyl-L-methionine which, in baboons, replenishes glutathione, and attenuates mitochondrial lesions. In addition, polyenylphosphatidylcholine (PPC) fully prevents ethanol-induced septal fibrosis and cirrhosis, opposes ethanol-induced hepatic phospholipid depletion, decreased phosphatidylethanolamine methyltransferase activity and activation of hepatic lipocytes, whereas its dilinoleoyl species increases collagenase activity. Current clinical trials with PPC are targeted on susceptible populations, namely heavy drinkers at precirrhotic stages.
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PMID:Ethanol metabolism, cirrhosis and alcoholism. 902 26

A continuously increasing production level in poultry breeding has resulted in changes in metabolism. Selection procedures in breeding programmes are focused on an increase in growth rate and on a decrease in feed conversion ratio (less feed intake per unit of deposited tissue). These procedures do not pay attention to the maintenance requirements of birds. Imbalances between production (protein and fat deposition) and supply of energy for maintenance requirements lead to homeostatic dysregulation and to diseases of organs which supply the energy for production and maintenance. The alarming increase in metabolic diseases, such as heart failure syndrome, ascites, and oedema in the lungs and heart, can be directly related to an insufficient oxygen supply. A low oxygen consumption and heat production is one of the mechanisms by which a low feed conversion ratio can be achieved, as is induced hypothyroidism by which physical activity and thus heat production is reduced. Other diseases, such as liver cirrhosis, malabsorption syndrome, sudden death syndrome in broilers, and fatty liver-hemorrhage syndrome, which is nowadays the most important disease in laying hens in the Netherlands, can be related to an imbalance between the production rate and maintenance requirements. A continued selection on the basis of retained energy (in protein and fat) without paying attention to the maintenance requirements of birds will be detrimental for the health and welfare of poultry. These undesirable developments in poultry husbandry should be a challenge for sciences focused on welfare and stress in animals. Such a scientific approach to animals suffering from dysgenic changes in metabolism is needed to solve serious problems in poultry breeding.
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PMID:Pathological changes in metabolism of poultry related to increasing production levels. 932 54


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