Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum concentrations were measured in individuals (n = 50) with liver diseases (cirrhosis and hepatitis) by hydride generation atomic absorption spectrometry in a cross-sectional study. Mean serum selenium levels determined in patients with cirrhosis (n = 12) or with hepatitis (n = 38) were significantly lower (P<0.01) than those measured in control groups mainly due to a decreased liver function. Mean serum selenium concentrations were significantly lower in cirrhotic individuals when compared with patients with hepatitis (P<0.05). Therefore, the severity of the live injury is a factor conditioning the impairment in the selenium body status observed in individuals with hepatopathies. In hepatic patients serum total cholesterol levels showed a significant correlation with serum selenium concentrations (r=0.912, P<0.05) demonstrating the important role of selenium as an antioxidant agent; similarly, gamma-glutamic-transferase levels were significantly correlated with the serum selenium levels (r=-0.803, P<0.05) indicating that when the intensity of the hepatic injury increases (enhancement in serum GGT levels) concomitantly the serum selenium levels decrease significantly. No significant relationships between serum selenium levels and sex or age of patients were observed.
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PMID:Selenium concentrations in serum of individuals with liver diseases (cirrhosis or hepatitis): relationship with some nutritional and biochemical markers. 1215 Apr 33

The effects exerted on hepatocytes by alcohol metabolites, drugs or other toxins and also hepatotropic viruses lead to chronic liver diseases. Reactive oxygen species (ROS) have been implicated in a number of pathologies, including different types of liver diseases. Organism has developed several mechanisms to counteract or prevent reactive oxygen species effects. These include enzymes such as: glutathione peroxidase (GSH-Px) with selenium (Se) in the active site and glutathione S-transferase (GST). Measurement of GST, compared with alanine aminotransferase (AIAT), has been advocated as a superior marker of hepatocellular damage. The aim of this study was to assess selenium concentration, glutathione peroxidase and glutathione S-transferase activities in plasma of patients with various types of liver diseases. The study population consisted of 54 patients and 25 healthy volunteers. The patients were divided into two groups according to etiology of the disease. Plasma selenium concentration was reduced in patients with cirrhosis, as compared to controls, irrespective of etiology and activity of AIAT. Plasma GSH-Px activity was significantly lower in both groups of patients with normal AIAT activity, whereas it was higher in both groups with activity of AIAT higher than 40 U/l. GST activity was higher only in post-viral group in patients with high AIAT activity. Impaired intestinal absorption and distribution of selenium among plasma proteins have been suggested as possible mechanism of reduced selenium concentration. Changes in the activities of glutatthione-dependent enzymes in plasma may arise from increased formation of reactive oxygen species or from release of these enzymes from injured hepatocytes to plasma.
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PMID:[Plasma selenium concentration, glutathione peroxidase and glutathione S-transferase activities in patients with chronic liver diseases]. 1255 39

Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P<0.001; plasma malondialdehyde (MDA), P=0.007] compared to age- and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P=0.013) and serum selenium and vitamin A were also lower (both P<0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of early-stage PBC.
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PMID:Oxidant stress is a significant feature of primary biliary cirrhosis. 1263 2

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.
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PMID:Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis. 1456 4

Epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx and the oesophagus and of the liver. The increased risk attributable to alcohol consumption of cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumours, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers is controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen but under certain experimental conditions is a cocarcinogen and/or tumour promoter. The metabolism of ethanol leads to the generation of acetaldehyde (AA) and free radicals. Evidence has accumulated that acetaldehyde is predominantly responsible for alcohol associated carcinogenesis. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, destructs folate and results in secondary hyperproliferation. Acetaldehyde is produced by tissue alcohol hydrogenases, cytochrome P 4502E1 and through bacterial oxidative metabolism in the upper and lower gastrointestinal tract. Its generation or its degradation is modulated due to functional polymorphisms of the genes coding for the enzymes. Acetaldehyde can also be produced by oral and faecal bacteria. Smoking, which changes the oral bacterial flora, and poor oral hygiene also increase acetaldehyde. In addition, cigarette smoking and some alcoholic beverages such as calvados contain acetaldehyde. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P-4502E1, which is associated with an enhanced production of free radicals and enhanced activation of various procarcinogens present in alcoholic beverages; in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens; alterations in cell cycle behaviour such as cell cycle duration leading to hyperproliferation; nutritional deficiencies, such as methyl-, vitamin E-, folate-, pyridoxal phosphate-, zinc- and selenium deficiencies and alterations of the immune system eventually resulting in an increased susceptibility to certain virus infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Also, an alcohol-mediated increase in oestradiols may be at least in part responsible for breast cancer risk. Thus, all these mechanisms functioning in concert actively modulate carcinogenesis leading to its stimulation.
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PMID:Alcohol and cancer. 1508 51

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology characterized by circulating autoantibodies, hyperglobulinaemia and interface hepatitis. The mechanisms of progression from initial autoimmune attack to fibrosis and cirrhosis are unclear but oxidant stress may be involved. Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood and urine in 35 controls and in 33 patients with type-1 AIH; histology was assessed in 18 patients. In AIH, markers of lipid peroxidation were significantly elevated (8-isoprostane in both plasma and urine P < 0.001; plasma malondialdehyde P = 0.017). Total antioxidant capacity in protein-free serum and total glutathione in both whole blood and plasma were significantly reduced (P = 0.007, P = 0.037, P < 0.001, respectively). The antioxidants selenium, vitamin A and vitamin E were significantly decreased (P = 0.007, P < 0.001, P = 0.025, respectively); vitamin C was unchanged. Urinary 8-isoprostane correlated positively with interface hepatitis and necroinflammatory score and with hepatic fibrogenesis (type III procollagen peptide). Interface hepatitis correlated negatively with vitamin A and whole blood total glutathione. Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of AIH and provides a probable mechanism linking hepatic necroinflammation to fibrogenesis and disease progression.
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PMID:Oxidant stress in type I autoimmune hepatitis: the link between necroinflammation and fibrogenesis? 1527 44

DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate.
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PMID:DNA methylation, cancer susceptibility, and nutrient interactions. 1552 34

The most important antioxidant aspect of selenium is its function in the active site of selenoenzyme glutathione peroxidase. Glutathione peroxidase not only allows the removal of the toxic radicals but also permits the regeneration of lipid molecules through reacylation in the cellular membrane. Thus, GSHPx may prevent the harmful effects of free radicals and may reduce the formation of the reactive metabolites of carbon tetrachloride. Carbon tetrachloride is a hepatotoxic agent which generates haloalkane radicals during its biotransformation in the liver and is widely used to make the experimental model of hepatic damage. Therefore, the aim of the present study is to investigate the possible protective role of selenium on the experimental liver cirrhosis and some enzyme activities in blood plasma from rats. While the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly increased (p < 0.05, p < 0.05 and p < 0.01, respectively), gamma-glutamyle transferase (GGT) activity was not statistically affected (p < 0.05) with carbon tetrachloride-injection. The levels of AST, ALT and GGT in carbon tetrachloride-group decreased to nearly the enzyme values in control-group after the selenium-injection but the ALP was increased (p<0.01). On the other hand, it was noticed that selenium significantly decreased the hepatic injury. In conclusion, our results showed that carbon tetrachloride caused an increase in the activities of liver enzymes in plasma and selenium application decreased the hepatic injury. Plasma levels of the liver enzymes were decreased after selenium-injections. Based upon these results, selenium may play an important role in the preventive indication of hepatic cellular injury inducted by carbon tetrachloride.
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PMID:Effects of selenium on histopathological and enzymatic changes in experimental liver injury of rats. 1558 Dec 76

Selenoprotein P is an abundant extracellular glycoprotein that is rich in selenocysteine. It has two domains with respect to selenium content. The N-terminal domain of the rat protein contains one selenocysteine residue in a UxxC redox motif. This domain also has a pH-sensitive heparin-binding site and two histidine-rich amino acid stretches. The smaller C-terminal domain contains nine selenocysteine and ten cysteine residues. Four isoforms of selenoprotein P are present in rat plasma. They share the same N terminus and amino acid sequence. One isoform is full length and the three others terminate at the positions of the second, third, and seventh selenocysteine residues. Selenoprotein P turns over rapidly in rat plasma with the consequence that approximately 25% of the amount of whole-body selenium passes through it each day. Evidence supports functions of the protein in selenium homeostasis and oxidant defense. Selenoprotein P knockout mice have very low selenium concentrations in the brain, the testis, and the fetus, with severe pathophysiological consequences in each tissue. In addition, those mice waste moderate amounts of selenium in the urine. Selenoprotein P binds to endothelial cells in the rat, and plasma levels of the protein correlate with prevention of diquat-induced lipid peroxidation and hepatic endothelial cell injury. The mechanisms of these apparent functions remain speculative and much work on the mechanism of selenoprotein P function lies ahead. Measurement of selenoprotein P in human plasma has shown that it is depressed by selenium deficiency and by cirrhosis. Selenium supplementation of selenium-deficient human subjects showed that glutathione peroxidase activity was optimized before selenoprotein P concentration was optimized, indicating that plasma selenoprotein P is the better index of human selenium nutritional status.
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PMID:Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. 1601 66

Nonalcoholic fatty liver disease (NAFLD) is becoming an increasing cause of chronic liver damage. The decision of start a medical treatment is based on the documented risk of progression to cirrhosis and liver cancer, when steatohepatitis (NASH) occurs. The therapy of this syndrome requires, as obviously, some considerations on the natural history of the condition, on the efficacy and safety of various therapeutic options, as well as on the costs. Treatment of patients with NAFLD has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipemia. Weight loss improves insulin sensitivity, and NASH may resolve with weight reduction. Insulin resistance seems to be the common denominator in many cases of NAFLD. Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone). The last two decades have witnessed a considerable progress in the understanding of the mechanisms respon-sible for the fibrogenic progression of chronic liver diseases. Several drugs believed to be hepatoprotective or antifibrotic agent as UDCA, betaine, vitamin E, lecithin, beta-carotene and selenium have been used in patients with NASH. Silybin is the main component of silymarin that is absorbed when linked whith a phytosome. This substance reduces in rats the lipid-peroxidation and the activaction of hepatic stellate cells. In humans, some non controlled data show that silybin is able to reduce insulin resistance, liver steatosis and plasma markers of liver fibrosis.
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PMID:The treatment of NAFLD. 1623 94


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