UMLS:C0015695 - FACTA Search

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

The ability of augmented antioxidant consumption to alter disease incidence, lesion burden and/or longevity was studied in adult male C57BL/6 mice. Mice were fed modified AIN76 diet or modified AIN76 supplemented with vitamin E, glutathione (GSH), vitamin E and GSH, melatonin or strawberry extract starting at 18 months of age. All the mice in this study were heavier than reference populations of male C57BL/6 mice fed NIH-07 or NIH-31, which were maintained without a mid-life change in diet. Fatty liver, focal kidney atrophy and proteinacious casts in the renal tubules were observed more frequently in this study population than in the reference populations. Lesion burden and incidence of specific lesions observed amongst the various groups in this study did not differ. There were no differences observed for longevity of any of the study groups. The longevity observed in this study was similar to that previously reported for male C57BL/6 mice. Thus, diet supplementation with antioxidants initiated during middle age did not appear to affect age-associated lesions patterns, lesion burden or longevity for ad libitum fed male C57BL/6 mice.
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PMID:Disease incidence and longevity are unaltered by dietary antioxidant supplementation initiated during middle age in C57BL/6 mice. 972 3

It is not known why viable hepatocytes in fatty livers are vulnerable to necrosis, but associated mitochondrial alterations suggest that reactive oxygen species (ROS) production may be increased. Although the mechanisms for ROS-mediated lethality are not well understood, increased mitochondrial ROS generation often precedes cell death, and hence, might promote hepatocyte necrosis. The aim of this study is to determine if liver mitochondria from obese mice with fatty hepatocytes actually produce increased ROS. Secondary objectives are to identify potential mechanisms for ROS increases and to evaluate whether ROS increase uncoupling protein (UCP)-2, a mitochondrial protein that promotes ATP depletion and necrosis. Compared to mitochondria from normal livers, fatty liver mitochondria have a 50% reduction in cytochrome c content and produce superoxide anion at a greater rate. They also contain 25% more GSH and demonstrate 70% greater manganese superoxide dismutase activity and a 35% reduction in glutathione peroxidase activity. Mitochondrial generation of H(2)O(2) is increased by 200% and the activities of enzymes that detoxify H(2)O(2) in other cellular compartments are abnormal. Cytosolic glutathione peroxidase and catalase activities are 42 and 153% of control values, respectively. These changes in the production and detoxification of mitochondrial ROS are associated with a 300% increase in the mitochondrial content of UCP-2, although the content of beta-1 ATP synthase, a constitutive mitochondrial membrane protein, is unaffected. Supporting the possibility that mitochondrial ROS induce UCP-2 in fatty hepatocytes, a mitochondrial redox cycling agent that increases mitochondrial ROS production upregulates UCP-2 mRNAs in primary cultures of normal rat hepatocytes by 300%. Thus, ROS production is increased in fatty liver mitochondria. This may result from chronic apoptotic stress and provoke adaptations, including increases in UCP-2, that potentiate necrosis.
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PMID:Mitochondrial adaptations to obesity-related oxidant stress. 1086 May 43

Although fatty liver (FL) is considered an innocuous condition, the frequent incidence of graft failure when FL are transplanted has renewed interest in the intracellular disorders causative of or consequent to fatty degeneration. Oxidative stress and nutritional status modulate the tolerance to reperfusion injury in control livers (CL), but very little is known in the case of FL. This study was designed to compare the oxidative balance in CL and FL from fed and food-deprived rats. Serum and liver samples were collected from fed and starved (18 h) rats with CL or FL induced by a choline-deficient diet. Hepatic injury was assessed by transaminase activities and histology. The hepatic concentrations of glutathione (GSH), vitamin C, alpha-tocopherol, thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (PC) were measured. Fed rats with FL had significantly greater TBARS and lower alpha-tocopherol and vitamin C levels than those with CL, whereas GSH and PC concentrations were not affected. Starvation impaired the oxidative balance in both groups. However, compared with the other groups, FL from food-deprived rats generally had the lowest hepatic concentrations of alpha-tocopherol, vitamin C and GSH. Unlike in CL, protein oxidation occurred in FL. These data indicate that fatty liver induced by consumption of a choline-deficient diet is associated with a lower level of antioxidants, which results in lipid peroxidation. Starvation further affects these alterations and extends the damage to proteins. In conclusion, steatosis and starvation may act synergistically on the depletion of antioxidants, predisposing fatty livers to a reduced tolerance to oxidative injury.
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PMID:Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet. 1095 3

Hepatic steatosis and the accompanying oxidative stress have been associated with a variety of liver diseases. It is not known if fat accumulation per se plays a direct role in the oxidative stress of the organ. This study tested if steatosis induced by a short-term carbohydrate-rich diet results in an increased hepatic sensitivity to oxidative stress. Antioxidant status was determined in a liver perfusion system and in isolated parenchymal, endothelial and Kupffer cells from rats kept on sucrose-rich diet or on regular diet for 48 h. t-Butyl hydroperoxide addition (2 mM) to the perfusion fluid resulted in a release of alanine aminotransferase (ALT) in livers from controls, whereas no ALT release was observed in fatty livers. After t-butyl hydroperoxide addition, oxidized glutathione release was 40% less in fatty than in control livers, whereas reduced glutathione (GSH) release was not different. Sinusoidal oxidant stress was mimicked by the addition of lipopolysaccharide (LPS) from Escherichia coli (10 microg/ml) followed by the addition of opsonized zymosan (8 mg/ml) to the perfusion medium. LPS plus zymosan treatments resulted in the release of ALT in control but not in fatty livers. At the end of perfusion, liver glutathione content was 3-fold elevated, and the tissue content of lipid peroxidation products was approx. 40% less in fatty livers compared to controls. GSH content was doubled and glucose-6-phosphate dehydrogenase (G6PD) expression was elevated by 3- and 10-fold in sinusoidal endothelial and parenchymal cells form fatty livers compared to cells from control animals. Following H(2)O(2) administration in vitro (0.2-1 mM), GSH remained elevated in endothelial and parenchymal cells from fatty livers compared to cells from controls. In contrast, G6PD activity and GSH content were similar in Kupffer cells isolated from fatty or control livers. The study shows that hepatic fat accumulation caused by a short-term sucrose diet is not accompanied by elevated hepatic lipid peroxidation, and an elevated hepatic antioxidant activity can be manifested in the presence of prominent steatosis. The diet-induced increase in G6PD expression and, thus, the efficient maintenance of reduced glutathione in endothelial and parenchymal cells are a supportive mechanism in the observed hepatic resistance against intracellular or sinusoidal oxidative stress.
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PMID:Augmented resistance to oxidative stress in fatty rat livers induced by a short-term sucrose-rich diet. 1101 71

In patients with severe alcoholic liver disease (i.e., cirrhosis), a deficiency of S-adenosylmethionine (SAMe) develops as a result of decreased SAMe synthetase activity. Whether a sizeable SAMe depletion occurs already at earlier stages of alcoholic liver disease has been the subject of debate. To address this issue, rats were fed alcohol (or isocaloric carbohydrate) in Lieber-DeCarli liquid diets containing adequate amounts of protein, vitamins, and lipotropic factors, including methionine. Alcohol feeding resulted in hepatic steatosis (without fibrosis) and unchanged SAMe synthetase activity, yet SAMe concentration was already greatly decreased. This most likely resulted from oxidative stress associated with the metabolism of alcohol and the induction of cytochrome P4502E1 (CYP2E1), which generates free radicals. Indeed, the decrease in hepatic SAMe correlated with parameters of oxidative stress, such as increased 4-hydroxynonenal (measured by gas chromatography-mass spectrometry) and diminished glutathione (GSH). Decreased GSH, occurring as a result of excessive GSH consumption caused by the oxidative stress, probably generated by enhanced utilization of SAMe, a precursor of GSH, thereby explaining the depletion of SAMe. In view of the known differences between rodents and primates in the metabolism of lipotropes, my colleagues and I have also studied the interaction between alcohol and SAMe in baboons and found again that, at early stages preceding the development of cirrhosis, there was already a significant lowering of hepatic SAMe concentration, associated with a striking oxidative stress documented by decreased levels and accelerated turnover of GSH. This was associated with increased lipid peroxidation and damage to cellular membranes, including those of the mitochondria, assessed by electron microscopy. Oral administration of SAMe resulted in its hepatic repletion with a corresponding attenuation of the ethanol-induced oxidative stress and liver injury, with significantly less GSH depletion, less increases in plasma aspartate aminotransferase (AST) levels, less leakage of mitochondrial glutamic dehydrogenase into the plasma, and fewer megamitochondria. In conclusion, (1) both in rodents and in non-human primates, significant SAMe depletion occurs already at early stages of alcoholic liver disease, despite the consumption of adequate diets; (2) the decreased hepatic SAMe concentration and the associated liver lesions, including mitochondrial injury, can be corrected with SAMe supplementation; and (3) accordingly, therapeutic administration of SAMe should be the subject of a comprehensive clinical trial to assess its capacity to attenuate early stages of alcoholic liver injury in human beings.
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PMID:S-Adenosyl-L-methionine and alcoholic liver disease in animal models: implications for early intervention in human beings. 1216 46

To study the influence of polymerised polyphenolics (PP), a fraction of silymarin (SM), on lipids and oxidant status, rats were fed high-cholesterol (1%), high-fat (10%) diets containing either lard fat (LFD) rich in saturated/monounsaturated fatty acids, or currant oil (COD) rich in polyunsaturated fatty acids. PP and SM were administered as dietary supplements (0.1-0.5-1.0%) for 3 weeks. PP (1%) decreased cholesterol (C) in VLDL (from 0.72+/-0.08 mmol l(-1) in LFD control to 0.35+/-0.07 mmol l(-1), P<0.01, and from 0.33+/-0.05 mmol l(-1) in COD control to 0.09+/-0.02 mmol l(-1), P<0.001), and increased HDL-C/VLDL-C ratio, however, without effect on the total plasma C and LDL-C. Liver C content (LFD 19.32+/-1.50 micromol g(-1), COD 18.64+/-2.13 micromol g(-1), N.S.) decreased after PP (1%) to 12.24+/-0.76 micromol g(-1), P<0.01, and 8.78+/-0.95 micromol g(-1), P<0.001, respectively. Triacylglycerols (TAG) in plasma and VLDL decreased after PP in the LFD group only, which displayed higher TAG levels than the COD group. Likewise, LFD caused a higher liver TAG content than did COD (31.16+/-3.00 micromol g(-1) versus 17.31+/-1.48 micromol g(-1), P<0.01), and PP (1%) decreased liver TAG only in rats fed LFD (19.55+/-2.43 micromol g(-1), P<0.02). Blood glutathione (GSH) increased after PP (1%) in the LFD group from 0.97+/-0.11 to 1.54+/-0.19 mmol l(-1) (P<0.05) and in the COD group from 0.58+/-0.15 to 1.23+/-0.10 mmol l(-1) (P<0.01), while liver GSH and plasma TBARS did not change. On principle, effects of PP were dose-dependent and parallel to SM. These results suggest that the polyphenolic fraction of SM positively modifies lipoprotein profile, counteracts the development of fatty liver and ameliorates an antioxidant status in circulation.
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PMID:Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets. 1252 57

Plant-based n-3 polyunsaturated fatty acids (PUFA) possess a prospective antiatherogenic potential. Currant oil from Ribes nigrum L. is one of the few plant oils containing PUFAn-3 (15.3 mol%) in addition to PUFAn-6 (60.5 mol%). This study was aimed at comparing the effects of currant oil with those of lard fat, rich in saturated (43.8 mol%) and monounsaturated (47.0 mol%) fatty acids, on antioxidant parameters, the lipoprotein profile and liver lipids in rats fed on 1 % (w/w) cholesterol diets containing either 10 % of currant oil (COD) or lard fat (LFD). After 3 weeks of feeding, the COD induced a significant decrease in blood glutathione (GSH) and an increase in Cu(2+) induced oxidizability of serum lipids, but did not affect liver GSH and t-butyl hydroperoxide-induced lipoperoxidation of liver microsomes. Although the COD did not cause accumulation of liver triacylglycerols as LFD, the lipoprotein profile (VLDL, LDL, HDL) was not significantly improved after COD. The consumption of PUFAn-3 was reflected in LDL as an increase in eicosapentaenoic and docosahexaenoic acid. These results suggest that currant oil affects positively the lipid metabolism in the liver, above all it does not cause the development of a fatty liver. However, adverse effects of currant oil on the antioxidant status in the blood still remain of concern.
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PMID:Antioxidant status, lipoprotein profile and liver lipids in rats fed on high-cholesterol diet containing currant oil rich in n-3 and n-6 polyunsaturated fatty acids. 1267 60

Four-aminopyrazolopyrimidine (4-APP)-induced fatty livers were studied immunohistochemically and biochemically. Immunohistochemical localization of glutathione-peroxidase (GSH-PO) in control rat liver was predominantly observed in the hepatocytes of portal zones of the hepatic lobules. After 3 days of 4-APP administration, the intensity of GSH-PO staining was weaker than that of control. Especially, this tendency was predominantly observed in portal zones of the hepatic lobules. Biochemcally, lipid peroxide levels measured by thiobarbituric acid method in the liver homogenates were markedly increased following 4-APP administration. However, glutathione-peroxidase (GSH-PO) activity in the same homogenates was decreased. Based on our data, we strongly suggested that pathogenesis of 4-APP induced-fatty liver may be due to uncontrolled free radical formation, peroxidation of lipids, and an associated lipid accumulation in the liver.
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PMID:Immunohistochemical and biochemical studies in 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver. 1270 44

We studied the effect of administering glycine on tissue lipid peroxidation and enzymic and non-enzymic antioxidants in experimental hepatotoxic Wistar rats. Hepatotoxicity was induced by administering ethanol for 30 days by intragastric intubation. Glycine administered at a dose of 0.6 g kg(-1) body weight for 30 days significantly inhibited the severe oxidative stress as evidenced by the decreased levels of liver and brain thiobarbituric acid reactive substances (TBARS) and hydroperoxides compared to control. The activities of enzymic and non-enzymic antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in the liver and brain were significantly elevated on glycine supplementation as compared to the untreated alcohol fed rats. The levels of serum vitamin E and vitamin C were also increased to near normal levels on glycine treatment. Microscopic examination of alcohol treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol treated rat brain demonstrated oedma, which was significantly lowered on treatment with glycine. Thus our study shows that administering glycine to alcohol supplemented rats, markedly reduced the oxidative stress and elevated the enzymic and non-enzymic antioxidants in the liver and brain, which a was associated with a reversal of hepatic steatosis and cerebral oedma.
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PMID:Effect of glycine on oxidative stress in rats with alcohol induced liver injury. 1496 23

The response of fatty liver to stress conditions (t-butyl hydroperoxide [t-BH] or 36 h of fasting) was investigated by assessing intracellular glutathione (GSH) compartmentation and redox status, GSH peroxidase (GSH-Px) and reductase (GSSG-Rx) activities, lipid peroxidation (TBARs) and serum ALT levels in rats on a choline-deficient diet. Baseline cytosolic GSH was similar between fatty and normal livers, while the mitochondrial GSH content was significantly lower in fatty livers. With the except of cytosolic GSH-Px activity, steatosis was associated with significantly higher GSH-related enzymes activities. Liver TBARs and serum ALT levels were also higher. Administration of t-BH significantly decreased the concentration of cytosolic GSH, increased GSSG levels in all the compartments, and increased TBARs levels in cytosol and mitochondria and serum ALT; all these alterations were more marked in rats with fatty liver. Fasting decreased the concentration of GSH in all the compartments both in normal and fatty livers, increased GSSG, TBARs and ALT levels, and decreased by 50% the activities of GSH-related enzymes. Administration of diethylmaleimide (DEM) resulted in cytosolic and microsomal GSH pool depletion. Administration of t-BH to DEM-treated rats further affected cytosolic GSH and enhanced ALT levels, whereas the application of fasting to GSH depleted rats mainly altered the mitochondrial GSH system, especially in fatty livers. This study shows that fatty livers have a weak compensation of hepatic GSH regulation, which fails under stress conditions, thus increasing the fatty liver's susceptibility to oxidative damage. Differences emerge among subcellular compartments which point to differential adaptation of these organelles to fatty degeneration.
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PMID:Adaptation of subcellular glutathione detoxification system to stress conditions in choline-deficient diet induced rat fatty liver. 1501 60

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