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)

Lysosome are subcellular particles in which several acid hydrolases of various specificities are localized. The role of lysosome in cellular physiology and pathology has drawn considerable recent attention by several groups of investigators. The purpose of this study was to investigate the activities of lysosomal enzymes--acid phosphatase, beta-glucuronidase, N-acetyl-beta-glucosaminidase--in hepatic disorders. 1) The serum levels of beta-glucuronidase and N-acetyl-beta-glucosaminidase were significantly elevated in patients with diseases of the hepatobiliary system. 2) N-acetyl-beta-glucosaminidase activity in urine specimens from patients with diseases of the hepatobiliary system was found to be significantly higher than in urine specimens from normal adults. 3) Male albino rats of 150 approximately 200 g body weight were used. CCl4 was injected intraperitoneally (dose 0.1 ml of CCl4 per 100 g body weight twice a week for eight weeks). The free activities of lysosomal enzyme were increased and high free/total activity ratios were found in the liver lysosomal fraction of CCl4 intoxicated rats. The results of these experiment indicated that the membranes of lysosome were more permeable to their enzymes, and the release of these enzymes were found in the experimental fatty liver by CCl4. 4) Corticosteroids and chloroquine stabilized rat liver lysosome in vitro from the labilizing influence of incubation at 37 degrees C. 5) The administration of chloroquine to CCl4 intoxicated rats did not cause any well-expressed stabilization of lysosomes. 6) When alpha-Tocopherol was administrated to CCl4 intoxicated rats, the decrease of bound activity and increase of free activity in lysosomal fraction, and increase of acid hydrolases, GOT and GPT in serum were inhibited.
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PMID:[Studies on lysosomes in hepatic disorders (author's transl)]. 48

Previous studies have shown that alpha-tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E-fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride-induced chronic liver damage and cirrhosis.
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PMID:Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis. 139 81

No published reports compare hepatic alpha-tocopherol (adjusted for hepatic lipid content) with indicators of blood alpha-tocopherol in adult patients with various liver diseases. alpha-Tocopherol was simultaneously measured in liver biopsy tissues and blood from 66 subjects (9 comparison patients hospitalized for biliary tract surgery, 13 with chronic persistent hepatitis, 9 with chronic aggressive hepatitis, 10 with acute hepatitis, 10 with cirrhosis, 7 with both cirrhosis and hepatic cell carcinoma, and 8 with fatty liver). Hepatic, erythrocyte, and plasma alpha-tocopherol concentrations were measured, as were hepatic and serum lipids. The ratios of alpha-tocopherol to total lipid concentrations (Toc/TL ratios) in plasma and liver were calculated. In both comparison patients and patients with chronic persistent hepatitis and fatty liver, hepatic alpha-tocopherol concentrations were strongly correlated with hepatic triglyceride and total lipid concentrations (r = .72, P < .001; and r = .75, P < .001, respectively); the relationships (slopes) when hepatic alpha-tocopherol concentrations were compared with hepatic triglyceride and total lipid concentrations were similar in these patients and in all subjects. No strong correlations were found between hepatic and blood alpha-tocopherol parameters in all subjects. These results suggest that hepatic alpha-tocopherol is present at similar concentrations in triglycerides as well as total cholesterol and phospholipids and that neither plasma Toc/TL ratios nor erythrocyte alpha-tocopherol concentrations are useful indicators of hepatic vitamin E status. The hepatic Toc/TL ratio may be useful to assess total hepatic vitamin E status.
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PMID:Assessment of hepatic vitamin E status in adult patients with liver disease. 925 50

The most common cause of hepatic fibrosis is currently chronic HCV infection, the characteristic feature of which is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also regarded as the primary target cells for inflammatory stimuli, and produce extracellular matrix components. It should be noted that transforming growth factor beta (TGF-beta) is a potent fibrogenic cytokine produced by Kupffer cells and HSCs. There are several approaches to inhibit TGF-beta; use of decorin, soluble receptors, and gene therapy approaches. Hepatocyte growth factor (HGF) is a hepatotrophic factor for liver regeneration and seems to suppress hepatic fibrogenesis in animals. HOE 77, Safironil, and S 4682 are inhibitors of prolyl 4-hydroxylase, which is essential for thecollagen formation. Although HOE 77, Safironil, and S 4682 seem to work by inhibiting HSC activation, further studies will be required before their clinical application. alpha-Tocopherol, retinyl palmitate, and silybinin reduce lipid peroxidation and attenuate HSC activation in experimental models. Retinyl palmitate is the main storage type for retinoids in HSCs. Silymarin is extracted from milk thistle, the principle component of which is the silybinin. Unfortunately, they have had mixed effects in human liver diseases. A Japanese herbal medicine Sho-saiko-to functions as a potent antifibrosuppressant via the inhibition of oxidative stress in hepatocytes and HSCs. Its active components are baicalin and baicalein of flavonoids with chemical structures very similar to silybinin. Understanding the basic mechanisms underlying the HCV-mediated fibrogenesis provides valuable information on the search for effective antifibrogenic therapies.
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PMID:Antifibrogenic therapies in chronic HCV infection. 1245 17

The cause of low fertility in dairy cows is multifactorial. Poor nutrition during the dry and early postpartum periods results in reduced glucose, insulin, insulin-like growth factor (IGF-I) and low LH pulse frequency with concomitant increases in beta-hydroxy butyrate, non-esterified fatty acids (NEFA) and triacylglycerol. Cows must mobilize large lipid, but also some protein reserves, with a consequent increased incidence of such metabolic disorders as hypocalcaemia, acidosis, ketosis, fatty liver and displaced abomasums. The occurrence of milk fever and ketosis affects uterine contractions, delays calving and increases the risk of retained foetal membranes (RFM) and endometritis. The nutritional risk factors that cause RFM are hypocalcaemia, high body condition score (BCS) at calving and deficiencies in Vitamin E and selenium. The risk factors for endometritis are hypocalcaemia, RFM, high triacylglycerol and NEFA. Thus, metabolic disorders predispose cows to gynaecological disorders, thereby reducing reproductive efficiency. Cows that are overconditioned at calving or those that lose excess body weight are more likely to have a prolonged interval to first oestrus, thereby prolonging days open. Nutritionally induced postpartum anoestrus is characterized by turnover of dominant follicles incapable of producing sufficient oestradiol to induce ovulation due to reduced LH pulse frequency. High nutrition can also increase metabolic clearance rate of steroid hormones such as progesterone or oestradiol. Lower concentrations of oestradiol on the day of oestrus are highly correlated with the occurrence of suboestrus, thereby making the detection of oestrus in high yielding cows even more difficult. Nutrition also affects conception rate (CR) to AI. Cows that develop hypocalcaemia, ketosis, acidosis or displaced abomasums have lower CRs and take longer to become pregnant. Excessive loss of BCS and excess protein content of the ration can reduce CR while supplemental fats that attenuate the production of F2alpha can improve CR. The increased metabolic clearance rate of progesterone (P4), which decreases blood concentrations during early embryo cleavage up to the blastocyst stage is associated with decreased CRs. In conclusion, poor nutritional management of the dairy cow, particularly before and after calving, is a key driver of infertility.
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PMID:The effect of nutritional management of the dairy cow on reproductive efficiency. 1699 5

Vitamin E (alpha-tocopherol) has demonstrated antioxidant activity and gene-regulatory properties. d-Galactosamine (D-GalN)-induced cell death is mediated by nitric oxide in hepatocytes, and it is associated with hepatic steatosis. The beneficial properties of alpha-tocopherol and their relation to oxidative stress and gene regulation were assessed in D-GalN-induced cell death. Hepatocytes were isolated from human liver resections by a collagenase perfusion technique. alpha-Tocopherol (50 microM) was administered at the advanced stages (10 h) of D-GalN-induced cell death in cultured hepatocytes. Cell death, oxidative stress, alpha-tocopherol metabolism, and NF-kappaB-, pregnane X receptor (PXR)-, and peroxisome proliferator-activated receptor (PPAR-alpha)-associated gene regulation were estimated in the hepatocytes. D-GalN increased cell death and alpha-tocopherol metabolism. alpha-Tocopherol exerted a moderate beneficial effect against apoptosis and necrosis induced by D-GalN. Induction (rifampicin) or inhibition (ketoconazole) of alpha-tocopherol metabolism and overexpression of PXR showed that the increase in PXR-related CYP3A4 expression caused by alpha-tocopherol enhanced cell death in hepatocytes. Nevertheless, the reduction in NF-kappaB activation and inducible nitric oxide synthase expression and the enhancement of PPAR-alpha and carnitine palmitoyl transferase gene expression by alpha-tocopherol may be relevant for cell survival. In conclusion, the cytoprotective properties of alpha-tocopherol are mostly related to gene regulation rather than to antioxidant activity in toxin-induced cell death in hepatocytes.
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PMID:Cytoprotective properties of alpha-tocopherol are related to gene regulation in cultured D-galactosamine-treated human hepatocytes. 1793 89

This study determined the effects of alpha- and gamma-tocopherol supplementation on metabolic control and oxidative stress in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Blood glucose, haemoglobin A1c (HbA1c), urinary protein, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) levels in OLETF rats were significantly higher than in non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. Alpha-tocopherol inhibited the increase in urinary protein, blood glucose, HbA1c and PAI-1 levels, but gamma-tocopherol did not. Plasma and hepatic lipid peroxidation and hepatic steatosis were increased in OLETF rats. alpha-Tocopherol decreased lipid peroxidation. Mitochondrial reactive oxygen species production and uncoupling protein 2 (UCP2) expression were significantly increased in the heart and aorta of OLETF rats compared with LETO rats. Endothelial NO synthase and aortic nitrotyrosine were increased in OLETF rats. In contrast, the expression of phosphorylated vasodilator-stimulated phosphoprotein and glucose transporter 4 in the aorta was significantly decreased in OLETF rats. These abnormalities were reversed by alpha-tocopherol. These findings suggest that alpha-tocopherol may prevent cardiovascular tissues from oxidative stress and insulin signalling disorder resulting from diabetes mellitus.
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PMID:Supplementation of alpha-tocopherol improves cardiovascular risk factors via the insulin signalling pathway and reduction of mitochondrial reactive oxygen species in type II diabetic rats. 1834 21

Nonalcoholic fatty liver disease (NAFLD) is a state of excessive accumulation of fat in the liver of persons whose alcohol intake is lower than the classical level for causing liver damage. When inflammation and fibrosis occur in addition to fatty liver, followed by the development of chronic hepatic dysfunction, the condition is called non-alcoholic steatohepatitis (NASH). Vitamin E possesses antioxidant activity and is effective for NASH, but the mechanism of action is not known. We utilized a methionine-choline deficiency rat model (MCD rats) to investigate the mechanism by which vitamin E improves NASH. In MCD rats, high-dose vitamin E therapy reduced the hepatic content of thiobarbituric acid-reactive substances, but failed to improve liver histopathology. The hepatic content of alpha-tocopherol was also elevated and this might be related to the expression of alpha-tocopherol transfer protein.
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PMID:Children's toxicology from bench to bed--Liver Injury (2): Mechanism of antioxidant therapy for nonalcoholic fatty liver disease. 1957 73

We have previously shown that treatment of steatotic livers with vitamin E succinate decreases liver injury and increases survival after ischemia/reperfusion (I/R). It is now understood that compromised energy status is associated with increased injury following liver ischemia in the setting of hepatic steatosis at least partially as a result of increased reactive oxygen species (ROS) and induction of mitochondrial uncoupling protein-2 (UCP2). Given the association between ROS, mitochondrial function, and UCP2, it was our goal to determine whether the protective effects of vitamin E succinate were associated with decreased ROS injury, down-regulation of UCP2, or improvement of ATP levels following I/R. To test this, leptin deficient (ob/ob) mice with steatotic livers that had received other 50 IU of vitamin E succinate supplement per day or control chow for 7 days were subjected to total hepatic ischemia (15 minutes) followed by reperfusion. We measured liver expressions of ATP, glutathione (GSH), and UCP2 as well as mitochondrial DNA damage. Vitamin E treatment decreased hepatic UCP2 expression and increased ATP and GSH levels prior to I/R. These levels were maintained at 1 hour after I/R. At 24 hours, while hepatic UCP2 expression, ATP, and GSH levels were similar to those of mice not receiving vitamin E, mitochondrial DNA damage was blocked. These results revealed that vitamin E succinate decreased hepatic UCP2 expression, reduced oxidative stress, and improved mitochondrial function in mice with steatotic livers before and after I/R, identifying mechanisms of protection in this setting.
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PMID:Vitamin E succinate enhances steatotic liver energy status and prevents oxidative damage following ischemia/reperfusion. 2000 47

Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD). NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH) is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only limited clinical evidence is available regarding their long-term efficacy and safety. Vitamin D and renin-angiotensin-aldosterone system blockers are promising drugs that are currently being intensively investigated for use in NAFLD/NASH patients.
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PMID:Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options. 2631 17


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