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

We have evaluated the efficacy of interferon-alpha (IFN-alpha) plus zinc therapy in hepatitis C patients with genotype 1b, poor responders for IFN alone. Ten patients were injected with 10 MU of IFN-alpha every day for 4 wk, followed by three times a week for 20 wk (control group). Nine patients took 300 mg of zinc sulfate a day orally during IFN-alpha therapy (zinc sulfate group), and 15 patients took IFN-alpha and 150 mg of polaprezinc (polaprezinc group). On the d 8 of IFN therapy, circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the zinc sulfate group or control group. Serum ALT levels normalized in 73.3% of the polaprezinc group, 55.6% of the zinc sulfate group, and 40.0% of the control group at 6 mo after the end of IFN therapy. Sustained eradication for the hepatitis C virus RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group (53.3% vs 11.1%, p < 0.05) or the control group (20.0%). No clinical side effects of zinc were observed at the dose used. The data suggest that polaprezinc is expected to increase the therapeutic response of IFN-alpha for chronic hepatitis C with genotype 1b.
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PMID:Preliminary study of combination therapy with interferon-alpha and zinc in chronic hepatitis C patients with genotype 1b. 1105 96

Metallothionein and zinc have been implicated in cellular defense against a number of cytotoxic agents. With respect to the free radical-generating hepatotoxin carbon tetrachloride, conclusions about a defensive role were reached from in vitro studies, in vivo studies using inducers of metallothionein and studies using injections of pharmacological amounts of zinc. Metallothionein knockout (null) and metallothionein transgenic mice are more direct models to examine the effects of metallothionein expression on induced cytotoxicity. Similarly, zinc presented via the diet is a more physiological model than that presented via injection. We examined whether metallothionein-overexpressing mice or metallothionein knockout mice had altered sensitivity to carbon tetrachloride and whether supplemental dietary zinc reduced sensitivity to carbon tetrachloride in these genotypes. Metallothionein knockout mice produced no metallothionein and were unable to sequester additional hepatic zinc in response to elevated dietary zinc. Hepatotoxicity, as measured by serum alanine aminotransferase activity, histological analyses and hepatic thiol levels, was greater in the knockout mice than in controls 12 h after carbon tetrachloride treatment but not at later time points (up to 48 h). In contrast, metallothionein-overexpressing mice produced more metallothionein and sequestered more liver zinc than control mice, but hepatotoxicity was similar between genotypes. Supplemental dietary zinc had no effect on hepatotoxicity with either genotype. These data suggest metallothionein null mice were more susceptible to carbon tetrachloride-induced hepatotoxicity than were control mice. However, neither metallothionein overexpression nor supplemental dietary zinc provided further protection.
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PMID:Metallothionein expression protects against carbon tetrachloride-induced hepatotoxicity, but overexpression and dietary zinc supplementation provide no further protection in metallothionein transgenic and knockout mice. 1116 May 36

The aim of this study was to investigate the effect of various medications other than interferon (IFN) on liver fibrosis in chronic hepatitis C (CH-C) patients, and the results were compared with those obtained in CH-C patients without therapy. Fifty CH-C patients (32 men and 18 women; mean age 58.5 years) without previous IFN therapy, who randomly received medicines other than IFN such as Stronger Neo-Minophagen C, Ursodeoxycholic acid and a herbal medicine, Sho-saiko-to (TJ-9) (Group I), and as a control group, 45 CH-C patients (27 men and 18 women; mean age 56.6 years) without therapy (Group II) were examined. All patients had persistent alanine aminotransferase (ALT) elevation more than 6 months before this study and were also subdivided into three subgroups according to different pattern of ALT during the observation period, i.e. (a): persistently ALT<60 IU/l (below about twice the upper limit of normal range); (b): persistently ALT>/=60 IU/l; and (c) other than (a) and (b). All patients were biopsied twice before starting this study and during observation period and the liver fibrosis was compared between them by staging in each case. When the fibrosis stage was the same between two specimens, we determined whether the degree of fibrosis had improved or worsened by computed image analysis. Blood tests for fibrosis marker, serum aminoterminal peptide of type III procollagen (P III P) and liver enzyme such as albumin (Alb) and zinc turbidity test (ZTT) levels, and platelet (Plt) counts were also examined on the two times of liver biopsy. As a result, there were no significant differences in fibrotic improvement rate when assessed by both staging only and staging together with fibrotic ratio, determined by computed image analysis and also in yearly change of P III P (P/Y) and fibrosis (F/Y), the changed rate of Alb, ZTT levels and Plt counts between Group I and Group II, except for P/Y in subgroup (a) which was rather higher in Group I than in Group II. There were also no significant relationship between the changes of histological activity and fibrosis staging in both groups. In conclusion, other medications than IFN could not significantly improve both liver fibrosis and its associated laboratory data irrespective of ALT levels in CH-C patients as compared to the control group during average 3 years' follow-up period.
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PMID:Does the control of alanine aminotransferase levels lead to a regression of liver fibrosis in chronic hepatitis C patients? 1116 39

To determine if nutrition plays a role in ethanol withdrawal and alcohol-induced brain damage, the effects of a 4-day ethanol binge treatment using ethanol in a nutritionally complete liquid diet compared to ethanol mixed with water were studied. The nutritionally complete diet group (ETOH-diet) received a complete diet of sugars, proteins and fats with vitamins and minerals with approximately 53% of calories from ethanol while the nutritionally deprived group (ETOH-H2O) received 100% of calories from ethanol. No difference in withdrawal behavior was found between the ETOH-diet and ETOH-H2O groups during the 72-hour period studied. In addition, no difference was seen for serum levels of magnesium and zinc taken at last dose or following 72 h of withdrawal. Serum alanine aminotransferase (ALT) and ammonia were increased in both groups with ETOH-diet showing a greater increase in ALT than ETOH-H2O. Both groups showed damage in the olfactory bulb, perirhinal, agranular insular, piriform and lateral entorhinal cortical areas as well as hippocampal dentate gyrus and CA-3. Interestingly, the ETOH-diet group displayed more damage at last dose in the posterior dentate and CA-3 of hippocampus than did the ETOH-H2O group. This study suggests that nutritional components and total caloric intake do not effect behavior during ethanol withdrawal and that a nutritionally complete diet may increase ethanol-induced brain damage.
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PMID:Interaction of nutrition and binge ethanol treatment on brain damage and withdrawal. 1117 87

Stress responses and changes in protein metabolism were studied in common carp Cyprinus carpio exposed to 0, 0.8, 4, and 20 microM cadmium (Cd) over a 29-day period. Blood and other tissue samples were taken after 4 and 29 days of exposure. The highest Cd concentration proved to be lethal to the fish, resulting in 100% mortality after 21 days of exposure. Cd accumulated in the tissues in the following order: kidney>liver>gills. Blood hematocrit, blood hemoglobin, plasma glucose, plasma lactate, and tissue total protein contents were not significantly altered. The concentrations of Cd and zinc (Zn) binding metallothioneins ((Cd, Zn)-MTs) were in the following order=liver>kidney>gills. An increase in (Cd, Zn)-MTs was observed at all exposure concentrations at days 4 and 29 in kidney and at Day 29 in gills. No significant changes in (Cd, Zn)-MT contents were found in liver. The concentrations of free amino acids and the activities of proteases were increased at Day 4 in gills, liver, and kidney of carp exposed to 4 and 20 microM Cd, and in gills and kidney at Day 29 in carp exposed to 4 microM Cd. The observed increases in the activities of aspartate aminotransferase and alanine aminotransferase suggest that the observed proteolysis is intended to increase the role of proteins in the energy production during Cd stress. However, this increased activity of both aminotransferases was not found in gills during exposure to the lethal Cd concentration, indicating that Cd may also cause an inhibitory effect on the activity of these enzymes above a certain level.
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PMID:Stress responses and changes in protein metabolism in carp Cyprinus carpio during cadmium exposure. 1122 34

Early effects of experimental cholestasis on the homeostasis of zinc (Zn) and metallothionein (MT) were studied in rats which had undergone bile duct ligation for 0, 3, 6, 9, 12, 16, 20, and 24 h. Transient increases in hepatic Zn levels were observed at 9 h but returned to control values at 12 h. Serum Zn levels increased at 24 h. Cholestasis was confirmed by increased serum alkaline phosphatase (AP) activity. MT increased at 3 h and reached a maximum level at 12 h and remained elevated even at 24 h after the onset of experimental cholestasis. No hepatocellular damage was detected according to the results of alanine aminotransferase (ALT) activities in serum. These results shown that the increases in Zn observed in liver are related to bile stagnation rather than to a hepatocellular damage and that increased MT occurs concurrently with increased hepatic Zn. These observations suggest that the cellular levels of Zn in cholestasis is regulated by homeostatic mechanisms, of which one could be mediated by MT.
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PMID:Effect of surgically induced cholestasis on the levels of hepatic zinc and metallothionein in rat liver. 1131 83

Reports in the literature indicate that the trifunctional amino acid D-penicillamine (D-P) induces a variety of muscle abnormalities, although the mechanisms are unknown. We hypothesised that defects may also arise due to the effects of D-P on rates of protein synthesis, possibly via changes in muscle metal composition. Male Wistar rats were injected with D-P at doses of 50 and 500 mg/kg body weight, i.p. Rats designated as controls were injected with 0.15 mol/l NaCl. After 24 h, there were reductions in muscle protein contents, protein synthetic capacities (RNA:protein ratio), fractional rates of protein synthesis, synthesis rates per unit RNA and synthesis rates per unit DNA in skeletal muscles of D-P treated rats. There were no statistically significant differences between the responses of the muscles containing a predominance of either Type I (represented by the soleus) or Type II (represented by the plantaris) fibres. In general, intracellular amino acids were not significantly affected by D-P treatment. Changes in muscle metals included significant reductions in copper, iron and manganese, without alterations in zinc or magnesium. In liver D-P reduced copper and iron though zinc, manganese and magnesium were unaffected. These effects of D-P on muscle may have been direct, as plasma indices of liver (activities of alkaline phosphatase and alanine aminotransferase) and kidney (urea, creatinine and electrolytes) damage were not significantly altered by D-P treatment. Plasma levels of corticosterone, insulin and free T3 were also not significantly affected by D-P treatment. Muscle protein carbonyl concentrations, an index of free radical activity, were similarly unaffected. This is the first report of reduced rates of muscle protein synthesis in D-P treatment. Our data suggests that the reduced rates of muscle protein synthesis may contribute to, or reflect, the muscle abnormalities observed in patients undergoing D-P treatment.
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PMID:Skeletal muscle protein loss due to D-penicillamine results from reduced protein synthesis. 1147 Feb 34

Relationships between hepatic antioxidant paraoxonase (PON1) activity, lipid peroxidation, and liver injury were investigated in rats with CCl(4)-induced cirrhosis. The study was performed in 60 CCl(4)-treated rats and 60 control animals receiving a standard diet or one supplemented with zinc. Subsets of 10 animals each were killed at weeks 1, 5, and 7 of the study. Results showed that PON1 significantly decreased in rats given CCl(4) alone compared with control animals. This effect was partially reversed in animals receiving zinc. Conversely, lipid peroxides were significantly increased in rats given CCl(4) alone and returned to approximately normal values in animals receiving zinc supplement. PON1 was inversely correlated with lipid peroxidation in all the animals studied. These alterations coincided with changes in serum alanine aminotransferase activity. In vitro incubation of isolated microsomes with CCl(4) or malondialdehyde did not produce any significant changes in PON1, indicating that the decrease in PON1 in CCl(4)-treated animals was not secondary to a direct inhibitory effect of lipid peroxidation products. These data show a time course and quantitative relationship between PON1 activity and lipid peroxidation in rats with CCl(4)-induced cirrhosis and suggest that this enzyme plays a significant role within the antioxidant systems in liver microsomes.
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PMID:Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. 1155 27

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide, and iron. HO-1, an inducible form, is thought to contribute to resistance to various types of oxidative stress. Doxorubicin (DOX) produces clinically useful responses in a variety of human cancers. We reported previously that prior administration of DOX ameliorated subsequent hepatic ischemia and reperfusion injury. The aim of this study was to examine whether this pharmacological preconditioning was useful for another type of hepatic injury induced by a non-surgical method. When a high dose of DOX (10 mg/kg body weight) was administered directly to rat liver via the portal vein, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels increased markedly 24 hr after the injection. Under this condition, zinc-protoporphyrin IX, a specific inhibitor of HO-1, caused both serum AST and ALT levels to be elevated further. When a low dose of DOX (5 mg/kg body weight) was administered to rats via the tail vein as pharmacological preconditioning 3 days before the injection of a high dose of DOX via the portal vein, the levels of serum AST and ALT in rats clearly were improved as compared with rats without the preconditioning. Expression of HO-1 in the liver was confirmed 3 days after the administration of a low dose of DOX. In addition, prior administration of zinc-protoporphyrin IX abolished the effect of DOX preconditioning. Immunohistochemical analysis showed that the positive staining of HO-1 protein induced by a low dose of DOX was localized to histiocytes infiltrating periportal areas. These results strongly suggest that pharmacological preconditioning with DOX may generally help to attenuate subsequent oxidant-induced hepatic injury.
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PMID:Pharmacological preconditioning with doxorubicin. Implications of heme oxygenase-1 induction in doxorubicin-induced hepatic injury in rats. 1170 58

Zinc (Zn) is an essential nutrient that is required in humans and animals for many physiological functions, including immune and antioxidant function, growth and reproduction. The present study was conducted to investigate the effects of adequate Zn level (38 mg/kg diet, as a control) and two low levels that create Zn deficiencies (19 mg/kg diet, 1/2 of the control and 3.8 mg/kg diet, 1/10 of the control) in growing male and female rats for 10 weeks. To evaluate the effects of these levels, the concentrations of thiobarbituric acid-reactive substances (TBARS), biochemical parameters and protein pattern were studied. Lipid peroxidation in liver, brain and testes of rats fed Zn-deficient diet was indicated by increased TBARS. Serum, liver, brain and testes glutathione S-transferase (GST) activities were significantly (P<0.05) increased in Zn-deficient rats, the effect was pronounced in rats fed the lowest level of Zn (1/10 of control). The activity of lactate dehydrogenase (LDH) was significantly (P<0.05) increased in liver, brain and testes, but decreased in serum in a dose-dependent manner. Zinc deficiency increased (P<0.05) liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in a dose-dependent manner, while there was no effect on the activity of these enzymes in testes. Zinc deficiency resulted in a significant (P<0.05) decrease in the activity of alkaline phosphatase (AlP) in serum and liver in a dose-dependent manner, but no effect in testes was found. The activity of acid phosphatase (AcP) was not affected in serum, liver and testes. Zn-deficient rats had higher liver concentrations of total lipids (TL), cholesterol, triglyceride (TG), and low density lipoprotein (LDL), while high density lipoprotein (HDL) was significantly (P<0.05) declined in a dose-dependent manner. Brain and serum acetylcholinesterase (AChE) activities were, however, not affected (P<0.05) by Zn deficiency. Protein content in liver, brain and testes showed a significant (P<0.05) decrease in rats fed the lowest level of Zn (1/10 of control). Polyacrylamide gel electrophoresis (native-PAGE) of serum proteins revealed that the intensity of immunoglobulins, serum albumin as well as several peptide bands were decreased in rats fed 1/2 or 1/10 of Zn adequate, i.e. their synthesis was affected and it was pronounced with the lowest level of Zn deficiency (1/10 of control). However, no clear effect on the transferrin was observed in both cases compared to controls. From the results of this study it can be concluded that Zn deficiency exerts numerous alterations in the studied biochemical parameters, protein pattern, and increased lipid peroxidation.
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PMID:Dietary zinc deficiency induced-changes in the activity of enzymes and the levels of free radicals, lipids and protein electrophoretic behavior in growing rats. 1204 50


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