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)

Micro-and macronodular experimental liver cirrhosis was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months, respectively. The glutathione (GSH) status (content, synthesis, export) and ultrastructural changes of liver were investigated 14 d after withdrawal of TAA. The hepatic level of GSH was increased after 6 months TAA treatment. The levels of oxidized glutathione (GSSG) were not changed after 3 months or 6 months TAA administration. The GSH synthesis was not disturbed in the cirrhotic livers; only the ratio between the 2 synthesizing enzymes was changed in macronodular liver cirrhosis. The plasma GSH content was reduced in both cases, independent of the stage of liver cirrhosis. The electron microscopic studies on cirrhotic rat livers revealed a series of characteristic structural changes, such as disorganization and total lack of the microvilli border, appearance of basement membrane-like deposits within the narrowed space of Disse, disappearance of the highly porous endothelial cell lining and partly an intensively detoriated blood supply within the pseudolobules. It is suggested that all these changes may contribute to a disturbance of the GSH export from the hepatocytes into the blood. It is very likely, however, that the alterations of the sinusoidal cell surface play the most important role. 1. The GSH/GSSG redox potential is shifted in favour of the reduced form in this cirrhosis model. This shift seems to be connected with later stages of cirrhogenesis. 2. A GSH export disturbance is responsible for the decreased plasma GSH level in liver cirrhosis.
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PMID:Glutathione synthesis and export in experimental liver cirrhosis induced by thioacetamide: relations to ultrastructural changes. 276 4

Liver glutathione-peroxidase (L-GSH-Px) and glutathione-reductase (GSSG-Red) activities were measured in supernatants of liver tissues obtained from a total of 36 subjects. Sixteen of these patients had a functionally normal liver (control group), whereas of the remaining 20 patients, 10 were cirrhotic and 10 had a liver disease other than cirrhosis. The mean value of L-GSH-Px of the control group was 33.12 +/- 12.66 U/g protein, a value similar to that found in patients with liver disease. The L-GSH-Px of the control group was positively correlated with the age of the subjects (r = 0.620; p less than 0.02). In contrast, in patients with liver disease an opposite behaviour of the two parameters was noted (r = -0.497; p less than 0.05). L-GSH-Px activity tended to be higher in males than in females, whereas the erythrocyte glutathione-peroxidase (E-GSH-Px) of the same patients was higher in females, albeit not significantly. L-GSH-Px and E-GSH-Px were not correlated either in normal or in liver disease. The mean GSSG-Red of the control group was 40.63 +/- 11.10 U/g protein, which is not different from that of the group of liver patients. GSSG-Red was not correlated with L-GSH-Px or with the age of patients. In two patients with hepatoma, the GSH-Px activity of the cancer tissue was low and the GSSG-Red activity high.
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PMID:Glutathione-peroxidase and glutathione-reductase activities of normal and pathologic human liver: relationship with age. 625 11

delta-Aminolevulinic acid dehydratase (ALAD) is the second enzyme in the heme biosynthetic pathway and catalyzes two molecules of delta-aminolevulinate (ALA), which is a potent agonist for GABA autoreceptors. ALAD has two common alleles and thus consists of three distinct isozymes, designated 1-1, 1-2, and 2-2. It has been shown recently that ALAD1 allele is associated with alcoholic liver injury. This association was ascribed to possible differences among isozymes in sensitivity to oxidized glutathione (GSSG), and this sensitivity is increased in erythrocytes of alcoholic patients. In the present study we measured erythrocyte ALAD activity from subjects with different ALAD genotype and found ALAD-1 is most sensitive to GSSG. We then investigated allele frequencies of ALAD in alcoholics (n = 126) and healthy controls (n = 115). For the control group, the frequencies were 0.94 (ALAD1) and 0.06 (ALAD2) and for the overall alcoholic group, 0.91 (ALAD1) and 0.09 (ALAD2). There were no significant differences in allele frequencies at the ALAD locus between the two groups. Subtyping the alcoholics according to the presence or absence of delirium tremens, hallucinosis, withdrawal seizure or liver cirrhosis failed to show statistically significant differences in the allele frequencies. We conclude that our data do not support the evidence of an allelic association between the ALAD1 and alcoholism.
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PMID:[Lack of association between alcoholism and alleles in the delta-aminolevulinic acid dehydratase (ALAD) gene]. 808 Apr

Plasma glutathione is markedly decreased in human cirrhosis of the liver. This decrease is said to be caused by reduced concentrations of liver glutathione. However, several studies on hepatic glutathione have revealed its concentrations to be unchanged, decreased, or even elevated. To test these inconsistencies we investigated the glutathione status of plasma, liver, and kidney in rats chronically exposed to carbon tetrachloride (CCl4). After 14 weeks of CCl4 treatment, histological examination revealed progressive cirrhotic transformation. After 20 weeks, complete micro-nodular cirrhosis was present and distinct ascites had developed. Plasma reduced glutathione (GSH) decreased by 34% in the early and by 44% in the late group, paralleled by a 65% and 76% decrease of plasma oxidized glutathione (GSSG). Liver GSH in early stages of cirrhosis was reduced by 49%, but in late cirrhosis it did not differ from controls. In contrast, liver GSSG increased by 35% in the early and by 191% in the late group. Kidney GSH increased by 14% in early and 44% in late stage cirrhosis. Kidney GSSG was unchanged in the early group, but increased by 18% in the late group. The decrease of plasma GSH and GSSG is closely related to the severity of experimental cirrhosis and inversely related to an increase of hepatic oxidized glutathione. The hepatic content of reduced glutathione, however, is decreased in early cirrhosis only. According to these results the inconsistent findings in man could be due to differences in the stages of cirrhosis in the patients. The increase in kidney glutathione is a new finding that needs further investigation, but it may probably be related to kidney dysfunction in liver disease.
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PMID:Glutathione in plasma, liver, and kidney in the development of CCl4-induced cirrhosis of the rat. 852 69

We do not know much about the changes that occur in reduced (GSH) and oxidized (GSSG) glutathione in the development of liver cirrhosis. Therefore, we investigated the glutathione redox system during development of liver cirrhosis after bile-duct ligation in rats. We compared the GSH and GSSG content of liver and plasma between bile-duct-ligated rats and sham-operated controls 6 and 24 h and 5, 15, 23, and 38 days after operation. Compared to controls (x +/- SD: 6.07 +/- 0.52 mumol/g wet wt.), liver GSH significantly increased 24 h (+ 37%) and 5 days (+ 53%) after bile-duct ligation. Thereafter, GSH continuously declined to 4.25 +/- 0.64 mumol/g (-31%; P < 0.001) at the end of the observation period after 38 days. The GSH turnover in 5-day bile-duct-ligated rats with high GSH concentrations was not significantly different than in sham-operated controls (16 nmol/min per g after bile-duct ligation and 15 nmol/min per g in controls). GSSG (211 +/- 42 nmol/g wet wt. in controls) was significantly lower 6 and 24 h after bile-duct ligation (-34% and -43%, respectively). Thereafter, GSSG increased and was about 100% higher than in controls after 23 and 38 days. The relation of GSSG to GSH in liver continuously increased from 3.4 to 20.5% after bile-duct ligation. The course of plasma GSH (9.57 +/- 0.79 mumol/l) paralleled hepatic GSH on a lower level: + 14% at day 5, -41% at day 15 and -51% at the end of the observation period. Plasma GSSG (0.99 +/- 0.31 mumol/l) was inversely related to liver GSSG: there were increased concentrations early after bile duct ligation (day 5: + 91%) and reduced concentrations (-44%) at the end of the observation period. Dynamic changes of the glutathione status occur in the development of liver cirrhosis after bile-duct ligation. These changes are consistent with increased oxidative stress in the liver and a deficit of transporting GSSG from the cells into plasma.
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PMID:Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation. 987 95

The aim of this study was to evaluate the effects of hepatitis B and C virus infections on liver glutathione status. Reduced and oxidized glutathione levels were determined in liver biopsy specimens obtained from patients with chronic liver disease including chronic active hepatitis and cirrhosis. In patients with hepatitis B virus infections, GSH and GSH/GSSG levels were significantly low compared with those in controls (P<0.01). There was a significant negative correlation between histological activity indices (HAI) and hepatic GSSG levels only in patients with chronic HCV infection (P<0.01; r=-0.895). In addition to this, we also found a positive correlation between indices (HAI) and GSH/GSSG of the same group (r=0.915; P<0.05). These observations suggest that HBV and HCV infections have different effects on liver glutathione status based on diverse mechanisms.
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PMID:The effects of chronic hepatitis C and B virus infections on liver reduced and oxidized glutathione concentrations. 1093 61

The aim of this study was to investigate mechanisms responsible for the inhibition of biliary glutathione efflux in rats with secondary biliary cirrhosis. Rats were studied after bile duct obstruction for 28 days. The biliary secretion of reduced glutathione (GSH), oxidised glutathione (GSSG) and cysteine were completely inhibited in biliary obstructed rats. Hepatic gamma glutamyltranspeptidase (gamma-GT) activity increased significantly, but following its inhibition by acivicin administration GSH, GSSG and cysteine were still absent in bile. Biliary obstruction resulted in a significant increase of the permeability of the paracellular pathway, as shown by the higher bile/plasma ratio and hepatic clearance of [14C]sucrose. GSH and GSSG were, however, significantly lower in the carotid artery and hepatic vein of obstructed animals and the arteriovenous difference across the liver was reduced. The concentration of GSH was significantly reduced and that of GSSG increased in the liver of obstructed rats. Biliary obstruction induced an increase in the hepatic concentration of cysteine and an inhibition of both gamma glutamylcysteine synthetase and methionine adenosyl transferase activities. Dichlorofluorescein (DCF) and the GSSG/GSH ratio and thiobarbituric acid reactive substances (TBARS) concentration, markers of reactive oxygen species production and lipid peroxidation, respectively, were significantly increased. Our data indicate that increased degradation or blood reflux of glutathione do not participate in the disruption of its secretion into bile and support the view that impairment of glutathione synthesis and oxidative stress could contribute to the decline in biliary glutathione output.
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PMID:Factors influencing the inhibition of biliary glutathione efflux induced by biliary obstruction. 1113 47

This study was conducted to develop a new biomaterial to be used for an antioxidative drug. In this study, the hepatoprotective effect of chondroitin sulfate (CS) (100 mg/kg and 200 mg/kg body weight) was investigated at the antioxidative enzyme levels of liver total homogenate and mitochondria fraction. And the carbone tetrachloride (CCl(4))-induced rats were used as hepatotoxic models. The CCl(4) induced rat has been widely used as a hepatotoxic model due to its practicality, convenience and cost effectiveness since the generation of free oxygen radicals by CCl(4) injection was proposed as an important causative agent of hepatotoxicity. Malondialdehyde (MDA) levels were determined as well as the activities of superoxide dismutase (SOD), catalase (CAT), reduced-glutathione (GSH), oxidized-glutathione (GSSG) and glutathione peroxidase (GPx) in the liver. In addition, histopathology of liver tissue was investigated. Liver antioxidative enzyme activity was elevated while MDA concentration was decreased in all CS treated animals. The results demonstrated that CS protected oxidative stress in a dose dependent manner. Moreover, inflammation and cirrhosis in liver tissue of CS treated group were significantly decreased. It gave us an impression that CS might be a radical scavenger.
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PMID:The effect of chondroitin sulfate against CCl4-induced hepatotoxicity. 1273 1

Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage to cells. Cells have a number of defense mechanisms to protect themselves from the toxicity of ROS. Mitochondria are especially important in the oxidative stress as ROS have been found to be constantly generated as an endogen threat. Mitochondrial defense depends mainly on superoxide dismutase (SOD) and glutathione peroxidase (GPx), whereas microsomal defense depends on catalase (CAT), which is an enzyme abundant in microsomes. SOD removes superoxide anions by converting them to H2O2, which can be rapidly converted to water by CAT and GPx. Also, GPx converts hydroperoxide (ROOH) into oxidized-glutathione (GSSG). Ovariectomized (OVX) rats are used as an oxidative stress model. An ovariectomy increased the levels of MDA, one of the end-products in the lipid peroxidative process, and decreased levels of the antioxidative enzymes; SOD, CAT and GPx. However, Chondroitin sulfate (CS) decreased the levels of MDA, but increased the levels of SOD, CAT and GPx in a dose-dependent manner. Moreover, inflammation and cirrhosis of liver tissue in CS- treated rats were significantly decreased. These results suggest that CS might be a potential candidate as an antioxidative reagent.
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PMID:Oxidative stress in ovariectomy menopause and role of chondroitin sulfate. 1546 Apr 50

It has been suggested that oxidative stress participates in the pathogenesis of hepatitis C virus infection. It also has been made clear that redox status in T cell and macrophage relates to the activity of virus infectious disease such as HIV infection. With such background we evaluated the relationship between the intracellular redox status of T cell and macrophage and the activity of HCV positive chronic liver disease. Intracellular GSH and GSSG levels of T cell and macrophage were determined in twenty-five HCV positive asymptomatic carriers (C-ASC), sixty-three chronic hepatitis patients (C-CH), ten HCV positive liver cirrhosis patients (C-LC) and twenty-nine healthy controls. The intracellular GSH levels of T cell (T-GSH) significantly decreased in both C-CH and C-LC compared with healthy controls. No significant differences in the T-GSH levels were found between healthy controls and C-ASC. T-GSH levels of C-CH and C-LC were significantly lower compared with C-ASC. The intracellular GSH levels of macrophage (CD14-GSH) of C-LC were significantly decreased compared with healthy controls. The CD14-GSH levels of C-CH and C-LC were significantly lower compared with C-ASC. There was no correlation between intracellular GSH, GSSG levels and the serum levels of iron-related markers, fibrogenesis markers and other clinical parameters. These results suggest that the intracellular redox status of T cell and macrophage relates to the progression of HCV related chronic liver disease.
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PMID:[The relationship between the intracellular redox status of immune cells and progression of hepatitis C virus related chronic liver disease]. 1555 20


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