Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidation of diethyldithiocarbamate (DTC) to disulfiram (DS) by liver microsomes was tested in vitro by using a copper-DTC chelate formation reaction after the conversion of DS to DTC by glutathione (GSH). In the presence of NADPH, microsomes produced DS from DTC in both the free and microsome-bound forms, the former being greater than the latter. DS production was dependent on NADPH and DTC concentrations, and incubation time. Increases in microsomal concentrations, up to a certain level, also increased the free and total DS production. NADH was only somewhat effective, both the exposure to a nitrogen atmosphere and heat-denaturation of the microsomes suppressed the reaction. Preincubation of microsomes with both DTC and NADPH markedly decreased aniline hydroxylase, p-nitroanisole O-demethylase and glucose-6-phosphatase activities, and moderately decreased NADH-ferricyanide and NADH-cytochrome c reductase, but NADPH-cytochrome c reductase was minimally affected. DTC alone had only slight effects on the activities. DS also decreased these enzyme activities, particularly glucose-6-phosphatase; the loss of NADPH-cytochrome c reductase activity being protected in the presence of NADPH. GSH almost completely prevented the loss of microsomal enzyme activities induced by DTC and NADPH except for the drug metabolizing activities, in which protection was incomplete. The microsomal oxidation of DTC to DS could play a role in the action of DS in the liver, since DS is rapidly degradated to DTC in vivo.
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PMID:Oxidation of diethyldithiocarbamate to disulfiram by liver microsomes in the presence of NADPH and subsequent loss of microsomal enzyme activity in vitro. 285 81

The effect on liver tissue of glutathione administration to rats treated for 7-14 days with 2-acetylaminofluorene was investigated. The DNA damage induced by the hepatotoxic agent and evaluated by the alkaline elution technique was significantly reduced by glutathione. Furthermore, GSH administration maintained liver GSH level, prevented the increase in alkaline phosphatase and reduced the decrease in glucose-6-phosphatase activity. GSH did not significantly influence the increase in gamma-glutamyl-transpeptidase and glutathione-S-transferase activities.
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PMID:Effect of glutathione on alterations of liver DNA structure and metabolic activities induced in vivo by 2-acetylaminofluorene. 288 May 50

Male Sprague-Dawley rats were fed a thiamine deficient diet for three weeks, then treated with a range of CCl4 doses (0.01-1-ml/kg). Rats fed the deficient diet grew more slowly (body weight 65 percent of control) and had elevated liver glutathione (GSH) (220 percent of control). CCl4 hepatotoxicity, assessed by serum glutamicpyruvic transaminase (SGPT) activity and histological examination 24 hours after the hepatotoxin, was augmented in the group fed the thiamine deficient diet. Likewise, CCl4 inhibition of liver endoplasmic reticulum (ER) function (glucose-6-phosphatase (G6Pase) and calcium pump activities one hour after CCl4) was enhanced in rats fed the deficient diet. These results suggest that thiamine deficiency enhances CCl4 damage to membranes of the ER and enhances CCl4 hepatotoxicity.
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PMID:Enhanced hepatotoxicity and inhibition of liver endoplasmic reticulum calcium pump by CCl4 in rats fed a thiamine deficient diet. 629 46

Adenosine proved to be an effective hepatoprotector increasing the survival rate of rats receiving lethal doses of CCl4. Searching for the mechanism of action, we found that adenosine transiently prevents the necrotic liver damage associated to an acute CCl4 treatment. The antilipoperoxidative action of the nucleoside was evidenced by a decrease of TBA-reactive products and the diene conjugates elicited by the hepatotoxin. Adenosine's protective effect was demonstrated by reverting the decrease of cytochrome P-450 while preserved intact the activity of the microsomal enzyme glucose-6-phosphatase. CCl4 promoted an increase in the oxidant stress through an enhancement in oxidized glutathione levels. This action was also completely counteracted by the nucleoside. Adenosine was unable to prevent CCl4 activation and, even, increased .CCl3 formation in the presence of PBN in vivo. However, in the presence of the nucleoside, irreversible binding of 14CCl4 to the microsomal lipid fraction of the treated animals was decreased. These results suggest that adenosine protective action might be exerted at the level of the propagation reaction following CCl4 activation. Two possible mechanisms were associated to the nucleoside protection: (1) the peroxide-metabolyzed enzymes, GSH-per, showed a marked increase after 30 minutes of adenosine treatment, which was potentiated by the hepatotoxin, suggesting an important role of this enzyme in the nucleoside's action; (2) the adenosine catabolism induced an increase in uric acid level, and allopurinol, a purine metabolism inhibitor, prevented such elevation as well as the antilipoperoxidative action of adenosine and the increase of GSH-per associated with the nucleoside treatment. These facts strongly suggest that the protective effect elicited by adenosine is not a direct one, but rather is related to its catabolic products, such as uric acid, which has been recognized as a free radical scavenger.
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PMID:Possible mechanism of adenosine protection in carbon tetrachloride acute hepatotoxicity. Role of adenosine by-products and glutathione peroxidase. 759 31

The effect of acute glutathione (GSH) depletion induced by GSH-depleting agent L-buthionine-(S,R)-sulfoximine (BSO) on hepatic microsomal glucose-6-phosphatase (G6Pase) activity in male Wistar rats was investigated. Liver GSH evaluated in high-performance liquid chromatography after administration of 4 mmol.Kg-1 BSO i.p. was decreased by 19% and 50% at the time-points of 1.5 h and 3 h, respectively. In these conditions, a significant decrease in Vmax and an increasing trend in K(m) of hepatic G6Pase activity were observed, especially in 3 h BSO-rats. Alterations in kinetic parameters of G6Pase were calculated in both intact and detergent-treated microsomes, using glucose-6-phosphate and pyrophosphate as substrate. A little increase in thiobarbituric acid-reactive substances and a limited decrease in 5,5'-dithiobis(2-nitrobenzoate)-reactive protein thiols were also noted. The results of this study show that acute GSH depletion induced by BSO is able to affect hepatic microsomal G6Pase activity. A possible explanation to account for the effect of BSO-induced GSH depletion on hepatic G6Pase system is discussed.
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PMID:Effects of acute glutathione depletion induced by L-buthionine-(S,R)-sulfoximine on rat liver glucose-6-phosphatase activity. 946 25

Temporal variation in metabolism and hepatotoxicity of acetaminophen (APAP) was examined using male ICR mice. Animals were injected with a single dose of APAP (400 mg/kg, i.p.) at 08:00, 14:00 or 20:00 h. APAP at this dose was markedly hepatotoxic to mice when administered at 20:00 h as determined by increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and by decreases in hepatic glucose-6-phosphatase (G-6-Pase) activity. However, mice appeared to be entirely insensitive to an identical dose of APAP given either at 08:00 or 14:00 h. Hepatic glutathione (GSH) level was significantly higher at 08:00, but no difference in GSH levels between 14:00 and 20:00 h was observed in normal mice. APAP and its metabolites in blood were monitored using HPLC for 3 h following the treatment. There were no significant differences in the plasma concentrations of APAP, APAP-glucuronide, APAP-sulfate, or APAP-mercapturate among the mice treated with this drug at 08:00, 14:00 or 20:00 h. However, the APAP-cysteine and APAP-GSH levels measured at 1 h following the APAP treatment were significantly lower in mice treated with this analgesic either at 14:00 or 20:00 h. In vitro hepatic microsomal p-nitrophenol hydroxylase activities were not different between 08:00, 14:00 and 20:00 h. But ethoxyresorufin O-deethylase and aminopyrine N-demethylase activities measured at 14:00 h were significantly lower than those of 08:00 or 20:00 h. Thus, the greater hepatotoxicity of APAP administered at 20:00 h appears to be related to the marked decrease in hepatic GSH at this time period, whereas the simultaneous reduction in APAP activation may be responsible for the lack of hepatotoxicity in mice treated with this analgesic at 14:00 h. These results suggest that the temporal variation in hepatotoxicity and metabolism of APAP is determined by interactions of multiple factors including the hepatic GSH level and drug metabolizing activities.
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PMID:Temporal variation in hepatotoxicity and metabolism of acetaminophen in mice. 970 5

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with diabetes mellitus (DM). Oil of Eruca sativa seeds (ESS) is tried for prevention and treatment of DM induced experimentally by alloxan injection. A single dose of alloxan (100 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides and cholesterol, decreased high-density lipoprotein and hepatic glycogen contents and elevated hepatic glucose-6-phosphatase activity. Concurrent with these changes, there was an increase in the concentration of malondialdehyde and 4-hydroxynonenal in the liver. This oxidative stress was related to a decreased glutathione (GSH) content and superoxide dismutase activity in the liver of alloxan-diabetic rats. ESS oil (0.06 ml/kg) on its own increased significantly hepatic GSH. Daily oral administration of ESS oil 2 weeks before or after diabetes induction ameliorated hyperglycemia, improved lipid profile, blunted the increase in malondialdehyde and 4-hydroxynonenal and stimulated the GSH production in the liver of alloxan-treated rats. We suggested that ESS oil could be used as antidiabetic complement in case of DM. This may be related to its antioxidative properties and to the increase in hepatic GSH.
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PMID:Amelioration of alloxan induced diabetes mellitus and oxidative stress in rats by oil of Eruca sativa seeds. 1105 94

The mechanisms responsible for the antidiabetic activity of both the white ginseng radix (Ginseng Radix Alba, GRA) and the rootlet (Ginseng Radix Palva, GRP) were investigated. After a four week oral administration, the fasting blood glucose levels in the GRA- and GRP-treated groups were lower when compared to the control group. To elucidate the hypoglycemic mechanism(s) of the ginseng radices, glucose absorption from the small intestine, hepatic hexokinase and glucose-6-phosphatase activities, in addition to PPAR-gamma expression in adipose tissue were examined. The results strongly suggest that GRA can improve hyperglycemia in KKAy mice, possibly by blocking intestinal glucose absorption and inhibiting hepatic glucose-6-phosphatase, and GRP through the upregulation of adipocytic PPAR-y protein expression as well as inhibiting intestinal glucose absorption.
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PMID:Comparisons between white ginseng radix and rootlet for antidiabetic activity and mechanism in KKAy mice. 1144 80

The present study was conducted to evaluate the therapeutic effectiveness of chelating agents [glutathione, 2,3 dimercapto propane sulfonic acid (DMPS) and D-penicillamine (DPA)] in combination with antioxidant (sodium selenite) in beryllium induced toxicity in female rats. A bolus dose of 50mg/kg-beryllium nitrate was administered singly followed by chelation therapy with GSH, DMPS + Se and DPA + Se at various durations of 1,3 and 7 days respectively. Results revealed a significant fall in the glycogen content, whereas, a marginal fall in the protein was also observed. The enzymatic activity of alkaline phosphatase and adenosine triphosphatase was depleted; on the contrary, there was a significant rise in the acid phosphatase and glucose-6-phosphatase pattern. A rise in the hepatic lipid peroxidation activity is a direct indication of oxidative damage resulting in free radical generation. The distribution of the metal by atomic absorption spectrophotometry revealed an increased concentration of beryllium in liver and kidney, followed by lung and uterus. The relative ability of three chelating agents to act as antagonists, for acute beryllium poisoning, have been examined in liver, kidney, lungs and uterus. The appreciable change in the beryllium concentration in various organs is duration dependent during the entire period being highly significant at 7 days regimen. Biochemical and distribution studies reveal that DPA + Se was the most effective therapeutic agent followed by DMPS + Se and GSH.
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PMID:Role of chelating agents and antioxidants in beryllium induced toxicity. 1262 5

The present study examines the effects of a hypercaloric diet on hepatic glucose metabolism of young rats, with and without monosodium glutamate (MSG) administration, and the association of these treatments with evaluating markers of oxidative stress. Male weaned Wistar rats (21 days old) from mothers fed with a hypercaloric diet or a normal diet, were divided into four groups (n=6): control (C) fed with control diet; (MSG) treated with MSG (4 mg/g) and control diet; (HD) fed with hypercaloric diet and (MSG-HD) treated with MSG and HD. Rats were sacrificed after the oral glucose tolerance test (OGTT), at 45 days of treatments. Serum was used for insulin determination. Glycogen, hexokinase(HK), glucose-6-phosphatase(G6PH), lipid hydroperoxide, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were determined in liver. HD rats showed hypoglycemia, hyperinsulinemia, and high hepatic glycogen, HK and decreased G6PH. MSG and MSG-HD had hyperinsulinemia, hyperglycemia, decreased HK and increased G6PH in hepatic tissue. These animals had impaired OGTT. HD, MSG and MSG-HD groups had increased lipid hydroperoxide and decreased SOD in hepatic tissue. Hypercaloric diet and monosodium glutamate administration induced alterations in metabolic rate of glucose utilization and decreased antioxidant defenses. Therefore, the hepatic glucose metabolic shifting induced by HD intake and MSG administration were associated with oxidative stress in hepatic tissue.
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PMID:Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue. 1466 76


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