Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl's stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16-7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6-18.65), and light to moderate ethanol intake (1-50 g/day) (OR, 5.22; 1.5-17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.
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PMID:Factors influencing the rate of fibrosis progression in chronic hepatitis C. 1562 36

Our objective was to determine the effect of serum iron levels and hepatic iron overload on hepatocellular damage in nonalcoholic steatohepatitis (NASH) and to compare this with chronic viral hepatitis. Twenty-five patients who had elevated transaminase levels on at least two occasions, without any evidence of viral and autoimmune hepatitis and diabetes, without a history of significant alcohol use, and with a liver biopsy consistent with NASH were enrolled in the study. Twenty-five patients with chronic viral hepatitis (13 patients with chronic hepatitis C and 12 with chronic hepatitis B) who were not under any antiviral treatment were taken as controls. Metabolic factors were studied in the NASH and chronic hepatitis groups. Biopsy specimens were stained with hematoxylin-eosin, and the grade of steatosis and the stage of fibrosis were evaluated as I, II, or III, I being mild and III being severe. Iron overload in the hepatic tissue was studied by Prussian blue staining. Serum ALT, AST, ALP, GGT, globulin, and ferritin levels were comparable in both steatohepatitis and chronic viral hepatitis groups. However, patients with chronic hepatitis had a lower albumin level and a higher serum iron level, with higher transferrin saturation. Among patients with NASH, mild, moderate, and severe steatosis was found in 7, 10, and 8 patients, respectively. Inflammatory infiltration was grade I in 24 patients and grade III in 1 patient. Fibrosis was mild in 12 patients and 13 patients had no fibrosis. Among patients with chronic viral hepatitis, inflammatory infiltration of grade I was seen in 11 patients, grade II in 11 patients, and grade III in 3 patients. Fibrosis was mild in 9 patients, moderate in 13 patients, and severe in 2 patients; 1 patient had no fibrosis. Compared to patients with NASH, those with chronic viral hepatitis cases had more severe inflammatory infiltration and fibrosis (P < 0.01). While five patients with chronic viral hepatitis had mild iron overload, patients with NASH had no hepatic paranchymal iron overload. Neither NASH nor chronic viral hepatitis revealed a relationship between hepatic iron overload and disease activity. This suggests that the iron overload actually may be a result of hemachromatosis gene mutation. The absence of hepatic parenchymal iron overload in the NASH group and only mild iron accumulation in the chronic hepatitis group may be explained by a lower frequency of the gene mutation in our country.
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PMID:Serum iron levels and hepatic iron overload in nonalcoholic steatohepatitis and chronic viral hepatitis. 1696 48

In this study, the possible potentiation of cisplatin-induced hepatotoxicity by cytochrome P450 2E1 (CYP2E1) was examined both in vitro and in vivo. Transfected HepG2 cells expressing CYP2E1 (E47 cells) and not expressing CYP2E1 (C34 cells) were used as an in vitro model, and mice drinking 2% acetone for 7 days to induce CYP2E1 were used as an in vivo model. Exposure of E47 cells to cisplatin caused a much greater loss of cell viability, more striking depletion of reduced glutathione (GSH), and higher reactive oxygen species (ROS) production as compared with C34 cells. The prooxidant L-buthionine-[R,S]-sulfoximine (BSO), which depletes GSH, enhanced cisplatin-induced loss of cell viability, whereas the antioxidant glutathione ethyl ester, or the iron chelator deferoxamine mesylate (DFO) protected against the cisplatin-induced loss of E47 cell viability. Diallyl sulfide (DAS), an inhibitor of CYP2E1, also protected against the cisplatin toxicity in the E47 cells. After being injected with cisplatin (ip, 45 mg/kg), mice drinking 2% acetone with increased CYP2E1 levels exhibited elevated levels of serum ALT and AST, liver caspase-3 activity and positive staining of TUNEL increased, and histopathology indicated the presence of necrotic foci in livers of acetone plus cisplatin-treated mice. Lipid peroxidation and protein oxidation as indicated by carbonyl formation, staining of 3-nitrotyrosine (3-NT) and iron were higher in the cisplatin plus acetone group, compared with cisplatin alone group. Both in vitro and in vivo results indicate that elevated CYP2E1 enhances cisplatin-induced hepatotoxicity, and the mechanism may involve increased production of ROS and oxidative stress.
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PMID:Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. 1625 82

Although liver injury is a recognized consequence of acute iron poisoning, its description is limited to several case reports. It appears to be dose-related, however, there are published reports of severe iron poisoning without liver injury. The purpose of this study is to examine the hypothesis that this is a dose-related phenomenon and to identify the serum iron concentration of risk for this outcome. The design of this study is a retrospective review of our hospital's experience over 20 years. Extracted data included demographics, time of ingestion, highest serum iron concentration and highest hepatic transaminase activity. Iron poisoning was defined as a serum iron concentration >300 microg/dL (55 micromol/L) within 12 hours of ingestion. Hepatotoxicity was defined as a serum transaminase (either ALT or AST) >150 U/L. Severe hepatotoxicity was defined >1000U/L. Seventy-three patients (1-48 years old) participated in the study and of these patients 60 (47 female) did not have hepatotoxicity. Their serum iron concentrations were 300-704 microg/dL (55-128 micromol/L). Thirteen patients had hepatotoxicity and of these patients, nine had severe liver injury. Severe injury was associated with serum iron concentrations well in excess of 1000 microg/dL (182 micromol/L). Our data support hepatotoxicity due to iron poisoning as a dose-related phenomenon with clinically important cases unlikely with a serum iron concentration of < 700 microg/dL (128 micromol/L) within the first 12 hours. Clinically important hepatotoxicity occurs with values in excess of 1000 microg/dL (182 micromol/L).
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PMID:Hepatotoxicity in acute iron poisoning. 1632 71

Heme oxygenase-1, a stress-responsive enzyme that catabolizes hemes into carbon monoxide, biliverdin, and iron, has been shown to play a pivotal role in many physiological and pathological situations. Here we investigated changes in HO-1 enzyme activity and protein expression, and its end product carbon monoxide concentrations in the liver of rats after CCl(4) treatment. We found that CCl(4) administration not only induced severe liver damage in rats, as demonstrated by dramatic elevation of ALT, AST levels and severe histopathological changes, but also resulted in a prominent up-regulation of HO-1 enzyme activity. Western blot and immunohistochemical analysis confirmed that expression of HO-1 protein was also increased significantly in a time-dependent manner following CCl(4) treatment, and localized mainly in liver cells around the central vein. In addition, CO concentrations in the liver of CCl(4)-treated rats were elevated remarkably in the same time-dependent way as HO-1 induction in contrast to the control rats. These data indicated that HO-1/CO pathway was greatly up regulated in the liver of rats after CCl(4) treatment, which might play an important protective role in the pathophysiological mechanism underlying CCl(4)-induced hepatotoxicity. It therefore suggested that more relevant studies should be carried out in the future to clarify the detailed mechanisms.
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PMID:Dynamic changes of heme oxygenase-1 and carbon monoxide production in acute liver injury induced by carbon tetrachloride in rats. 1697 57

Liver function tests include biochemical parameters (AST, ALT, GGT or Alkaline phosphatase), bilirubin and albumin levels and coagulation tests as prothrombin activity. These tests are commonly used in the routine screening even in symptomatic as in asymptomatic patients, and the right evaluation of the results is of vital importance. Cytolytic elevation in serum aminotransferases: In mild chronic elevation pharmacological toxicity, viral hepatitis, alcoholic and non-alcoholic fatty liver disease and hemochromatosis, should be excluded. Cholestatic elevation os serum enzymes: The first option should be to establish the origin of the alkaline phosphatase elevation, with the evaluation of the GGT levels to confirm the hepatic origin. The next step should be to distinguish the presence of an extrahepatic (biliary obstruction) or intrahepatic (PBC, PSC, drugs, etc) cholestasis, in these cases the most important test should be the abdominal ultrasound, in order to evaluate the biliary system. Hyperbilirubinemia: Non conjugated hyperbilirubinemia (hemolysis, ineffective erythropoiesis, Gilbert or Criggler-Najjar syndromes) and conjugated hyperbilirubinemia, an unusual situation in which Rotor and Dubin-Johnson Syndromes should be considered. The evaluation of albumin and prothrombin levels evaluates the hepatic function per se, allowing to differentiate between acute and chronic diseases. At present, there are not prospective studies to evaluate the efficacy of the liver function tests. To carry out a complete medical history, an appropriate physical examination and the appropriate application of non-invasive diagnostic tests (serology, iron levels, autoimmunity or abdominal ultrasound) allow to perform a right diagnosis in most patients, making more complex tests, including liver biopsy, secondary.
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PMID:[Utility of analytical parameters in the diagnosis of liver disease]. 1737 60

Co-administration of iron in combination with monoisoamyl dimercaptosuccinic acid (MiADMSA) against chronic arsenic poisoning in mice was studied. Mice preexposed to arsenic (25 ppm in drinking water for 6 months) mice were treated with MiADMSA (50 mg/kg, intraperitoneally) either alone or in combination with iron (75 or 150 mg/kg, orally) once daily for 5 days. Arsenic exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, hematocrit, and white blood cell (WBC) counts accompanied by small decline in blood hemoglobin level. Hepatic reduced glutathione (GSH) level, catalase and superoxide dismutase (SOD) activities showed a significant decrease while, oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS) levels increased on arsenic exposure, indicating arsenic-induced hepatic oxidative stress. Liver aspartate and alanine transaminases (AST and ALT) activities also decreased significantly on arsenic exposure. Kidney GSH, GSSG, catalase level and SOD activities remained unchanged, while, TBARS level increased significantly following arsenic exposure. Brain GSH, glutathione peroxidase (GPx), and SOD activities decreased, accompanied by a significant elevation of TBARS level after chronic arsenic exposure. Treatment with MiADMSA was marginally effective in reducing ALAD activity, while administration of iron was ineffective when given alone. Iron when co-administered with MiADMSA restored blood ALAD activity. Administration of iron alone had no beneficial effects on hepatic oxidative stress, while in combination with MiADMSA it produced significant decline in hepatic TBARS level compared to the individual effect of MiADMSA. Renal biochemical variables were insensitive to any of the treatments. Combined administration of iron with MiADMSA also had no additional beneficial effect over the individual protective effect of MiADMSA on brain oxidative stress. Interestingly, combined administration of iron with MiADMSA provided more pronounced depletion of blood arsenic, while no additional beneficial effects on tissue arsenic level over the individual effect of MiADMSA were noted. The results lead us to conclude that iron supplementation during chelation has some beneficial effects particularly on heme synthesis pathway and blood arsenic concentration.
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PMID:Combined administration of iron and monoisoamyl-DMSA in the treatment of chronic arsenic intoxication in mice. 1745 51

Non-ceruloplasmin bound copper ('free') seems slightly elevated in Alzheimer's disease (AD) patients. To test the hypothesis of a correlation between 'free' copper and liver function in AD. We evaluated 51 AD patients and 53 controls through typical tests for chronic liver disease (AST, ALT, gamma-GT, Albumin, prothrombin time - PT-, bilirubins), along with copper, ceruloplasmin, iron, cholesterol in the serum and apolipoprotein E epsilon4 (APOE4) genotype. Absolute serum copper and 'free' copper were higher, albumin was lower and PT longer in AD patients than in controls. 'Free' copper correlated negatively with markers of liver function, in that albumin and albumin/PT ratio (r = -0.43, p = 0.004), and positively with direct bilirubin. Copper and 'free' copper were higher in the APOE4 carriers. These results suggest that abnormalities in copper metabolism might have an effect on liver function in AD.
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PMID:'Free' copper in serum of Alzheimer's disease patients correlates with markers of liver function. 1764 16

The aim of the study is to evaluate the serum copper, ceruloplasmin and 24-h urine copper levels in celiac patients. Serum copper, ceruloplasmin and 24-h urine measurements were evaluated in patients with celiac (n = 32), Crohn's (n = 25), Wilson's (n = 11) and in a healthy group (n = 35). Serum and 24-h urine zinc levels, AST, ALT, BUN, creatinine, iron, hemoglobin, hematocrit, lymphocyte, sedimentation and CRP levels were also measured. Results were evaluated statistically and significance was accepted as meaningful if P < 0.05. In celiacs, levels of urine copper were high (52 +/- 29 microg/day, P < 0.000) but serum copper was the same as in controls (105 +/- 16 microg/dl, P < 0.158). High urinary copper of celiacs were coming out in women (56 +/- 30 microg/day) and in man (33 +/- 17 microg/day, P < 0.115). Most celiacs were female (P < 0.001). Serum copper and ceruloplasmin levels in all groups were higher in women than in men and this was meaningful for serum copper in the control group (P < 0.045) and for ceruloplasmin in Crohn's (P < 0.055) and control groups (P < 0.031). Serum (70 +/- 14 microg/dl, P < 0.000) and urine zinc levels (25 +/- 15 microg/dl, P < 0.039) of celiacs were low. Ceruloplasmin levels were higher in celiacs (337 +/- 64 U/1) and Crohn's patients (366 +/- 47 U/l, P < 0.000). Correlations observed in the groups of celiac (P < 0.029) and Crohn's (P < 0.024), celiac and Wilson's (P < 0.001) and Crohn's and Wilson's (P < 0.001) between the ceruloplasmin and 24-h urine copper parameters. AST and ALT levels were higher in celiac and Wilson's patients than in Crohn's patients and controls. Mean CRP levels were significantly higher in Crohn's than others. Lymphocyte counts were meaningfully higher in celiacs. Statistically, while mean iron, hemoglobulin and hematocrit levels of celiac and Crohn groups were meaningfully lower than the normal and Wilson's group, it was similar in Wilson's and the control group. Serum copper (85 +/- 26 microg/dl, P < 0.158) and ceruloplasmin (219 +/- 83 U/l, P < 0.001) levels were low and 24-h urine copper levels were high (415 +/- 346 microg/day) in Wilson's group. Increased urinary loss may be another cause of copper deficiency in female celiacs besides malabsorption and this topic needs more investigation. Increased urinary copper levels in celiac women should not always be regarded as a diagnosis of Wilson's disease.
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PMID:Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients. 1793 56

Transplantation of primary human hepatocytes is a promising approach in certain liver diseases. For the visualization of the hepatocytes during and following cell application and the ability of a timely response to potential complications, a non-invasive modality for imaging the transplanted cells has to be established. The aim of this study was to label primary human hepatocytes with micron-sized iron oxide particles (MPIOs), enabling the detection of cells by clinical magnetic resonance imaging (MRI). Primary human hepatocytes isolated from 13 different donors were used for the labelling experiments. Following the dose-finding studies, hepatocytes were incubated with 30 particles/cell for 4 hrs in an adhesion culture. Particle incorporation was investigated via light, fluorescence and electron microscopy, and labelled cells were fixed and analysed in an agarose suspension by a 3.0 Tesla MR scanner. The hepatocytes were enzymatically resuspended and analysed during a 5-day reculture period for viability, total protein, enzyme leakage (aspartate aminotransferase [AST], lactate dehydrogenase [LDH]) and metabolic activity (urea, albumin). A mean uptake of 18 particles/cell could be observed, and the primary human hepatocytes were clearly detectable by MR instrumentation. The particle load was not affected by resuspension and showed no alternations during the culture period. Compared to control groups, labelling and resuspension had no adverse effects on the viability, enzyme leakage and metabolic activity of the human hepatocytes. The feasibility of preparing MPIO-labelled primary human hepatocytes detectable by clinical MR equipment was shown in vitro. MPIO-labelled cells could serve for basic research and quality control in the clinical setting of human hepatocyte transplantation.
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PMID:Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography. 1841 May 23


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