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)

In the companion paper we demonstrated that hepatic vitamin E in rats becomes depleted and extrahepatic pools of vitamin E are altered by treatment with 1,2-dibromoethane (DBE). Vitamin E depletion may be dependent upon initial steps of DBE metabolism that are either oxidative (cytochrome P450 dependent) or conjugative (glutathione transferase dependent). That the liver content of glutathione (GSH) and vitamin E, the plasma concentration of vitamin E, and the serum activities of AST and ALT may be influenced by cytosolic metabolism of DBE was assessed by comparison of findings from rats treated with either 1,2-dichloroethane (DCE) or 1-bromo-2-chloroethane (BCE). The extent of oxidative metabolism was diminished by the use of tetradeutero-DBE (d4-DBE), and the availability of GSH for conjugative metabolism was diminished by pretreatment of rats with L-buthionine-S,R-sulfoximine (BSO) prior to treatment with DBE. Our results indicate that neither DCE nor BCE provokes a liver vitamin E depletion in rats, that d4-DBE treatment hastens but does not enhance the observed hepatic vitamin E depletion by comparison to animals treated with an equimolar dose of DBE, and that BSO pretreatment prevented the hepatic vitamin E depletion observed from animals treated with DBE alone. These results indicate that hepatic vitamin E depletion is the unique sequelae to conjugation of GSH with DBE, and we suggest the reactive episulfonium ion intermediate or a macromolecular adduct of this ion derived from DBE may play a role in liver vitamin E depletion associated with exposure to DBE.
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PMID:Modification of hepatic vitamin E stores in vivo. III. Vitamin E depletion by 1,2-dibromoethane may be related to initial conjugation with glutathione. 189 41

The effects of chronic ethanol intake on the levels of alpha-tocopherol and gamma-tocopherol in serum and liver of both vitamin E-deficient and normal rats were studied. An intragastric feeding rat model was used. Both normal and vitamin E-deficient animals were fed a liquid diet and ethanol for 1 month. In pair-fed animals, dextrose was isocalorically replaced by ethanol. The blood ethanol level in the ethanol-fed animals was between 150 and 250 mg/dL. Liver peroxidation was determined by measuring thiobarbituric acid reactive substances (TBARS). Plasma alanine aminotransferase (ALT) was increased by 3-fold in vitamin E-deficient ethanol-fed rats compared with normal ethanol-fed rats. Plasma alpha- and gamma-tocopherol were decreased in the normal ethanol-fed rats by 22.3 and 65%, respectively (P < 0.01). Liver alpha- and gamma-tocopherol were also decreased by 51.7 and 76%, respectively (P < 0.01). Vitamin E-deficient animals had significantly lower mean plasma alpha-tocopherol (5670 vs 530 ng/mL, P < 0.01), and ethanol feeding did not decrease the levels any further. However, ethanol feeding decreased liver alpha- and gamma-tocopherol by 58.5 and 56.5% (P < 0.01), respectively, beyond the already low levels observed in this group. There was an inverse correlation between liver TBARS and liver alpha-tocopherol (r = -0.59, P < 0.05) and gamma-tocopherol (r = -0.65, P < 0.02). Also of significance is that ethanol feeding decreased the plasma and liver gamma-tocopherol more than the alpha-tocopherol in both normal and vitamin E-deficient animals. In conclusion, ethanol feeding markedly decreased both alpha- and gamma-tocopherol in livers of normal and vitamin E-deficient rats, but it only decreased plasma levels of tocopherols in normal rats. The higher ALT in vitamin E-deficient animals and the inverse correlation between TBARS and alpha- and gamma-tocopherol suggest that enhanced lipid peroxidation is associated with greater severity of liver injury induced by ethanol in vitamin E-deficient rats.
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PMID:Effect of chronic ethanol feeding on plasma and liver alpha- and gamma-tocopherol levels in normal and vitamin E-deficient rats. Relationship to lipid peroxidation. 801 Sep 85

Effect of glutathione (GSH) depletion on paraquat (PQ) toxicity in the liver and kidneys of mice was examined. Glutamic-pyruvate transaminase (GPT) and blood urea nitrogen (BUN) levels in plasma of mice were hardly changed by treatment with 150 micro mol/kg of PQ. However, significant increases in the plasma GPT and BUN levels after PQ injection were observed in mice which were pretreated with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, at 4 hr prior to PQ administration. This result supports the previous observation that hepatotoxicity of PQ was enhanced in diethyl maleate-pretreated mice (Cagen and Gibson, 1977). In the present study, lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBA-RS) level in the liver of mice given PQ was elevated by pretreatment with BSO. Moreover, enhancement of PQ cytotoxicity by BSO pretreatment was also observed in cultured mouse hepatoma cell line (NCTC clone 1469). Vitamin E, an antioxidant, and Desferal, an iron chelator, significantly prevented mice from the BSO-enhanced hepato- and nephrotoxicity of PQ. These findings suggest that the tissues or cells of low GSH concentration are highly vulnerable to PQ toxicity and GSH may play a major role in diminishing the toxic action of PQ exerted through oxidative stress.
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PMID:Enhancement of paraquat toxicity by glutathione depletion in mice in vivo and in vitro. 872 Jan 62

RRR-alpha-Tocopherol (Vitamin E) was assayed in plasma of 48 patients with viral hepatitis and of 32 healthy controls. In patients with highly elevated serum transaminases (ALT > 100 U/L) vitamin E plasma levels were significantly lower (17.5 +/- 4.8 mumol/L) than in controls (22.7 +/- 4.2 mumol/L, p < 0.01). The vitamin E/lipid ratios (3.12 +/- 0.63 mumol/g) in these patients were 33% lower than those of the controls (4.68 +/- 0.54 mumol/g). The lowered vitamin E levels in patients with acute or chronic viral hepatitis with high activity of disease may be due to free radical-mediated liver injury.
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PMID:Diminished plasma levels of vitamin E in patients with severe viral hepatitis. 895 19

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-alpha-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged >65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyroglobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation.
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PMID:Assessment of the safety of supplementation with different amounts of vitamin E in healthy older adults. 970 Nov 88

The aim of this investigation was to determine serum levels of vitamin A, E, beta carotene, glutathione peroxidase (GSHPx), lipid peroxidation (MDA) and biochemical and haematological parameters during enflurane anaesthetised dogs. Ten kangal dogs were used and all animals were anaesthetised with enflurane for two hours and blood samples were taken before and 30, 120 minutes, 24 hours and 7 days during the anaesthesia. Vitamin E and beta carotene content were significantly (p<0.05 and p<0.01) higher before anaesthesia than after whereas serum GSHPx activity was not statistically different. However, serum levels of vitamin A and MDA were significantly (p<0.05) increased during the anaesthesia. In general, serum levels of aspartate aminotransferase, alanine aminotransferase, albumin, glucose, urea and creatinine were significantly (p<0.05 and p<0.01) increased during anaesthesia and returned to near normal values after 7 days of anaesthesia, whereas the white blood cell count was significantly (p<0.05 and p<0.01) decreased during the anaesthesia. However, the red blood cell count, haemoglobin and packed cell volume values, and levels of total cholesterol, triglycerides, total protein and globulin were apparently not influenced by the anaesthesia. In conclusion, we observed that the serum level of vitamin E and beta carotene were significantly decreased, whereas serum MDA and vitamin A levels were significantly increased during the enflurane anaesthesia.
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PMID:The levels of some antioxidant vitamins, glutathione peroxidase and lipoperoxidase during the anaesthesia of dogs. 1045 42

The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3 x 4.5 million units IFN-alpha 2a per week), (group A), or IFN and N-acetylcysteine (N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 microg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05-5.5) of obtaining a complete response and had significantly greater reduction in viral load (P = 0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.
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PMID:Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial. 1051 13

The objective of this study was to determine the effects of supplementation of ascorbic acid, Vitamin E (Vit. E) and their combination in drinking water on sperm characteristics, lipid peroxidation (LPO) and seminal plasma enzymes of mature male rabbits. Twenty-four male New Zealand White rabbits (5 months old) were given drinking water supplemented with ascorbic acid (1.5 g/l), Vit. E (1.0 g/l) and ascorbic acid+Vit. E (1.5+1.0 g/l) for 12 weeks. Vitamin supplementation in drinking water increased feed intake, but body weight gain was not significantly affected. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly (P<0.05) reduced in seminal plasma of treated groups compared with the control. Treatment with ascorbic acid, Vit. E, and their combination significantly (P<0.05) increased lipido (reaction time), ejaculate volume, sperm concentration, total sperm output, sperm motility index, total motile sperm, packed sperm volume, initial hydrogen ion concentration (pH), and semen initial fructose concentration. Abnormal and dead sperm were significantly (P<0.05) decreased in treated animals. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly (P<0.05) decreased, whereas glutathione S-transferase (GST) showed a significant increase in seminal plasma of treated animals compared with the controls. The results from this study indicated that supplementation of drinking water with antioxidant ascorbic acid, Vit. E and their combination reduced the production of free radicals and can improve rabbit semen quality, but the greater improvement seemed to be from Vit. E.
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PMID:Effect of ascorbic acid and Vitamin E supplementation on semen quality and biochemical parameters of male rabbits. 1255 24

The presence of cyanobacterial toxins in drinking and recreational waters represents a potential public health risk. Microcystin-LR (MC-LR) is a potent cyclic heptapeptide hepatotoxin produced by the blue-green alga Microcystis aeruginosa. Chemoprotectant studies have indicated that membrane-active antioxidants such as vitamin E may offer protection against microcystin toxicity. This study investigated the effect of vitamin E supplementation on microcystin toxicity in mouse liver. Groups of mice were fed vitamin E supplements (8.33 or 33.3 U/mouse/day) for 4 weeks, with intraperitoneal doses of MC-LR extract (70% LD(50)) every 3 days from day 8. The potential benefits of vitamin E were evaluated based on lipid peroxidation, alanine transaminase (ALT), and glutathione S-transferase (GST) levels. Vitamin E supplementation at 33.3 U/mouse/day offered some protection against lipid peroxidation induced by repeated exposure to MC-LR extract and limited both the toxin-induced increase in ALT leakage and decrease in GST activity. Vitamin E supplementation at 66.6 U/mouse/day significantly increased the time to death and reduced the increase in liver percentage body weight induced in mice given a lethal dose challenge of MC-LR extract. Therefore, vitamin E, taken as a dietary supplement, may have a protective effect against chronic exposure to MC-LR.
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PMID:An investigation of the role of vitamin E in the protection of mice against microcystin toxicity. 1263 3

Previous studies have implied a relationship between Se-deficiency and oxidative stress. In the present study, the occurrence of oxidative stress due to Se-deficiency was investigated by evaluating the age dependence of growth and indices of oxidative damage for the liver of Se-deficient (SeD) rats. The ratios of liver weight to body weight of the SeD rats were greater than those of the normal rats. The values of AST and ALT (clinical indices of liver damage) were higher in the SeD rats than the normal ones especially in the young (6-12 weeks of age). The TBARS level of the 4-week-old SeD group were higher than the normal group while the level decreased with age. Conversely, the TBARS level of the normal group gradually increased and became higher than SeD group in older rats (12-20 weeks of age). Vitamin E rather than vitamin C may be consumed during oxidative stress due to Se-deficiency. Damage induced by Se-deficiency may be related to growth and the mechanisms of this damage may alter with age.
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PMID:Evaluation of oxidative damage in the liver of selenium-deficient rats. 1268 28


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