Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcoholic liver disease (ALD) in Japan was compared clinicopathologically with the occurrence in the U.S.A. ALD found in Japan was more frequently complicated by other hepatic diseases including non-A, non-B chronic hepatitis than ALD found in the U.S.A. (9.9% versus 21.9%). Patients with such complications were excluded from this study. The chief complaints of the total of 51 alcoholics studied in the U.S.A. were abdominal distension or jaundice and those of 98 alcoholics studied in Japan were non-specific: general fatigue, weakness or appetite loss. The U.S. patients exhibited more elevated levels of serum bilirubin (8.1 +/- 7.5 versus 1.9 +/- 2.4 mg/dl, mean +/- SD) and a higher incidence of leukocytosis (49.0% versus 5.1%). While the serum glutamic-oxalacetic transaminase (GOT) levels were not significantly different between the two groups (146.5 +/- 116.8 versus 140.8 +/- 147.7 IU/L), the serum glutamic-pyruvic transaminase (GPT) levels among Japanese alcoholics were higher (38.6 +/- 31.4 versus 87.4 +/- 99.1 IU/L) and in about one quarter of these patients, serum GPT was higher than serum GOT, a feature not seen in the patients in the U.S.A. Comparative histopathologic study of 337 U.S. patients and 210 Japanese patients disclosed a higher frequency of cirrhosis (46.9% versus 33.8%), the presence of Mallory bodies (58.5% versus 13.8%) and marked neutrophilic exudation (45.1% versus 6.2%). Thus, the majority of Japanese alcoholics exhibited progression of liver disease, eventually leading to cirrhosis, due to hepatocellular drop-out and fibrosis caused by a mechanism different from alcoholic hepatitis. In addition, ALD in the U.S.A. revealed more striking extension of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The characteristics of alcoholic liver disease in Japan. Clinicopathologic comparison with alcoholic liver disease in the United States. 369 16

We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken together, these results suggest that vitamin K may have a role in the mechanism of PIVKA-II elevation in sera of these patients. Then, we measured serum concentrations of vitamin K(PK, MK-4, MK-7) in these patients. There was no correlation observed between vitamin K and PIVKA-II in these patients. This result suggests that elevation of serum PIVKA-II in these patients may not be due to vitamin K deficiency. One question not answered here is how serum PIVKA-II levels in these patients are suppressed by treatment with vitamin K (Kaytwo). More detailed analysis of the mechanism of elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis is needed.
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PMID:[Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis]. 1198 59

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism and folate deficiency. Because folate is integral to the methionine cycle, its deficiency could promote alcoholic liver disease by enhancing ethanol-induced perturbations of hepatic methionine metabolism and DNA damage. We grouped 24 juvenile micropigs to receive folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE and FDE) for 14 wk, and the significance of differences among the groups was determined by ANOVA. Plasma homocysteine levels were increased in all experimental groups from 6 wk onward and were greatest in FDE. Ethanol feeding reduced liver methionine synthase activity, S-adenosylmethionine (SAM), and glutathione, and elevated plasma malondialdehyde (MDA) and alanine transaminase. Folate deficiency decreased liver folate levels and increased global DNA hypomethylation. Ethanol feeding and folate deficiency acted together to decrease the liver SAM/S-adenosylhomocysteine (SAH) ratio and to increase liver SAH, DNA strand breaks, urinary 8-oxo-2'-deoxyguanosine [oxo(8)dG]/mg of creatinine, plasma homocysteine, and aspartate transaminase by more than 8-fold. Liver SAM correlated positively with glutathione, which correlated negatively with plasma MDA and urinary oxo(8)dG. Liver SAM/SAH correlated negatively with DNA strand breaks, which correlated with urinary oxo(8)dG. Livers from ethanol-fed animals showed increased centrilobular CYP2E1 and protein adducts with acetaldehyde and MDA. Steatohepatitis occurred in five of six pigs in FDE but not in the other groups. In summary, folate deficiency enhances perturbations in hepatic methionine metabolism and DNA damage while promoting alcoholic liver injury.
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PMID:Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. 1212 4

Patients suffering from Alcoholic Liver Diseases (ALD) are often diagnosed by spectrum of physical manifestations and laboratories abnormalities. Among biochemical abnormalities De Ritis Ratio (AST/ALT ratio) is more sensitive during any phase of the disease. This ratio is based on common tests of liver function test and can be investigated in any laboratory and is more relevant in countries like Nepal where alcohol abuse is a major cause of liver disease. Clinically diagnosed 103 ALD cases and 73 healthy controls were enrolled for the study. Selected parameters of liver function tests were analyzed by Vitalab Selectra-2 autoanalyser using Merck diagnostic kits and statistically analyzed by student "t" test. The De Ritis ratio was calculated from serum AST and ALT values and was found 2. 30:1 in patients compared to of 1.10:1 in control group. AST and ALT value showed mild to moderate elevation as it was 124.80 +/- 86.24 IU/L and 54.21 +/- 39.72 IU/L in patients compared to 35.00 +/- 23.49 IU/L and 31.48 +/- 17.79 IU/L in controls. The increase in AST and ALT level in patients was statistically significant (p < 0.001) and (p < 0.01) respectively. > or = - Glutamyl Transferase showed 425.26 +/- 36.40 IU in alcoholics compared to 70.55 +/- 27.35 IU/L in controls, a significant increase observed (p<0.001) However Alkaline Phosphatase activity was observed within normal limit. Serum Total Protein (TPR) and Albumin (ALB) showed 6.86 +/- 1.01 g/dl and 2.71 +/- 0.78 g/dl in patients with Albumin: Globulin ratio of 0.61:1 compared to 7.51 +/- 1.74 g/dl and 4.03 +/- 0.61 g/dl in controls with the ration of 1.15:1, a significant decrease in albumin (p < 0.001) without alteration of Total Protein in patients. Total and Direct bilirubin showed 2.32 +/- 1.10 mg/dl and 1.26 +/- 0.88 mg/dl in alcoholics higher than the control of 1.06 +/- 0.60 mg/dl 0.38 +/- 0.31 mg/dl (p<0.001). Diagnosis of ALD is straight forward with history-and compatible clinical features but alcoholic's denial and under estimation of alcohol abuse becomes an obstacle in confirmation. A mild to moderate disproportionate elevation of AST than ALT activity making De Ritis Ratio > 2:1, supported by reversal of Albumin/globulin ratio facilitates the diagnosis.
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PMID:De Ritis ratio as diagnostic marker of alcoholic liver disease. 1682 89

Alcoholic liver disease and hepatitis C are associated with the production of autoantibodies such as rheumatoid factors (RF), which bind to IgG and can aid in host defence, but are also associated with pathological conditions such as rheumatoid arthritis. Because little is known about the role of RF in liver disease, we characterized the RF production that either occurred spontaneously in response to alcohol consumption or was induced by injection of an Escherichia coli glycolipoprotein in C57Bl/6 mice. Whereas severe liver damage was induced by carbon tetrachloride (CCl(4)), minimal damage was caused by chronic alcohol consumption. Liver damage was monitored by measurements of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Circulating RF was induced in response to chronic alcohol consumption; the latter probably involved Toll-like receptor ligation. In contrast, CCl(4)-induced damage was not associated with RF induction. However, concurrent treatment with an E. coli glycolipoprotein macromolecule that induced RF, protected against CCL(4)-induced liver damage as measured by a highly significant decrease (P = 0.008) at 4 weeks in AST and ALT. RF induced by E. coli glycolipoprotein correlated with 'protection' from liver damage, indicating that the RF autoimmune response does not necessarily exacerbate liver disease.
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PMID:Rheumatoid factor induction in murine models of liver injury. 1722 74

Alcoholic liver disease (ALD) is one of the most common diseases in society. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of ALD. 2-Hydroxy-4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India, is expected to significantly inhibit the development of liver injury in ethanol administration. It is expected to reduce the severity of liver damage in terms of body weight, hepatic marker enzymes, oxidative stress, antioxidant status and histological changes in ethanol-induced hepatotoxic rats. Hepatotoxicity was induced by administering 20% ethanol (5 g kg(-1) daily) for 60 days to male Wistar rats, which resulted in significantly decreased body weight and an increase in liver-body weight ratio. The liver marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase were elevated. In addition, the levels of plasma, erythrocyte and hepatic thiobarbituric acid reactive substances, hydroperoxides and conjugated dienes were also elevated in ethanol-fed rats as compared with those of the experimental control rats. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C and alpha-tocopherol was also observed on alcohol administration as compared with experimental control rats. HMBA was co-administered at a dose of 200 mug kg(-1) daily for the last 30 days of the experiment to rats with alcohol-induced liver injury, which significantly increased body weight, significantly decreased the liver-body weight ratio, transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase, significantly decreased the levels of lipid peroxidative markers, significantly elevated the activity of enzymic and non-enzymic antioxidants in plasma, erythrocytes and liver and also increased levels of plasma and liver vitamin C and alpha-tocopherol at the end of the experimental period as compared with untreated ethanol-administered rats. The histological changes were also in correlation with the biochemical findings. The results suggest that HMBA administration may afford protection against ethanol-induced liver injury in rats.
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PMID:Antioxidant effect of 2-hydroxy-4-methoxy benzoic acid on ethanol-induced hepatotoxicity in rats. 1733 49

Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.
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PMID:Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats. 1828 59

Alcoholic liver disease is multifactorial and oxidative stress is believed to play an intimate role in the initiation and progression of this pathology. The goals of this study were to investigate the effect of chronic ethanol treatment on inducing hepatic oxidative stress and peroxiredoxin 6 expression. After 9 weeks of treatment with an ethanol-containing diet, significant increases in serum ALT activity, liver to body weight ratio, liver triglycerides, CYP2E1 protein expression, and CYP2E1 activity were observed. Chronic ethanol feeding resulted in oxidative stress as evidenced by decreases in hepatic glutathione content and increased deposition of 4-hydroxynonenal and 4-oxononenal protein adducts. In addition, novel findings of decreased PRX6 protein and mRNA and increased levels of carbonylated PRX6 protein were observed in the ethanol-treated animals compared to the pair-fed controls. Lastly, NF-kappaB activity was found to be significantly increased in the ethanol-treated animals. Concurrent with the increase in NF-kappaB activity, decreases in both MEK1/2 and ERK1/2 phosphorylation were also observed in the ethanol-treated animals compared to the pair-fed controls. Together, these data demonstrate that chronic ethanol treatment results in oxidative stress, implicating NF-kappaB activation as an integral mechanism in the negative regulation of PRX6 gene expression in the mouse liver.
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PMID:Decreased expression of peroxiredoxin 6 in a mouse model of ethanol consumption. 1885 41

Alcoholic liver disease (ALD) is a major medical complication of drinking alcohol, and commonly accompanied with hepatic iron overload and liver injuries. Oxidative stress plays an important role in pathogenesis of ALD and also leads to iron-metabolic disorders. In this study, the effects of vitamin C (Vc) on iron metabolism-related genes expression and liver protection from drinking in mice were investigated. Twenty-four male kunming mice were divided into four groups (six mice per group): control (water drinking); alcohol group (20% alcohol drinking), alcohol + low Vc group (adding 50 mg/kg Vc daily) and alcohol + high Vc group (adding 100 mg/kg Vc daily). All these mice were sacrificed after 7 days. Vc can ameliorate the increase of sera alanine aminotransferase (ALT) activity and hepatic iron overload of drinking alcohol in mice. Vc increases the expression of the iron-regulated hormone hepcidin and decreases transferrin receptor 1 (TfR1) expression in liver. Vc also down-regulates the expression of ferroportin 1 (Fpn1) in the intestine and decreases the iron release to blood. In conclusion, Vc ameliorated the alcoholic liver injuries through regulating the iron metabolism-related genes expression.
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PMID:Vitamin C protective role for alcoholic liver disease in mice through regulating iron metabolism. 2107 91

Alcoholic liver disease is caused mainly by free radicals. Ascorbic acid (AA) and glutathione (GSH) are the major water-soluble antioxidants in the liver. The impact of AA supplementation on GSH, AA and activities of GSH-dependent enzymes in alcoholic guinea pigs was studied and was compared with alcohol abstention. Guinea pigs were administered ethanol at a dose of 4 g/kg body weight (b.wt)/day for 90 days. After 90 days, alcohol administration was stopped and one-half of the ethanol-treated animals were supplemented with AA (25 mg/100 g b.wt) for 30 days and the other half was maintained as the abstention group. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase in the serum of the ethanol group. In addition, a significant decrease in the GSH content, activities of GSH peroxidase, GSH reductase, and increased activity of GSH-S-transferase were observed in the liver of the ethanol group. Histopathological analysis and triglycerides content in the liver of the ethanol group showed induction of steatosis. But AA supplementation and abstention altered the changes caused by ethanol. However, maximum protective effect was observed in the AA-supplemented group indicating the ameliorative effect of AA in the liver.
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PMID:Ascorbic acid supplementation causes faster restoration of reduced glutathione content in the regression of alcohol-induced hepatotoxicity in male guinea pigs. 2256 50


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