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:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the hypothesis that thallium (Tl) interactions with the glutathione-dependent antioxidant defence system could contribute to the oxidative stress associated with Tl toxicity. Working in vitro with reduced glutathione (GSH), glutathione reductase (GR) or glutathione peroxidase (GPx) in solution, we studied the effects of Tl+ and Tl3+ (1-25 microM) on: (a) the amount of free GSH, investigating whether the metal binds to GSH and/or oxidizes it; (b) the activity of the enzyme GR, that catalyzes GSH regeneration; and (c) the enzyme GPx, that reduces hydroperoxide at expense of GSH oxidation. We found that, while Tl+ had no effect on GSH concentration, Tl3+ oxidized it. Both cations inhibited the reduction of GSSG by GR and the diaphorase activity of this enzyme. In addition, Tl3+ per se oxidized NADPH, the cofactor of GR. The effects of Tl on GPx activity depended on the metal charge: Tl+ inhibited GPx when cumene hydroperoxide (CuOOH) was the substrate, while Tl(3+)-mediated GPx inhibition occurred with both substrates. The present results show that Tl interacts with all the components of GSH/GSSG antioxidant defence system. Alterations of this protective pathway could be partially responsible for the oxidative stress associated with Tl toxicity.
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PMID:In vitro interactions of thallium with components of the glutathione-dependent antioxidant defence system. 1562 16

Quercetin and galangin can change the activity of glutathione reductase. Quercetin (a catechol structure in the B-ring) and galangin (any hydroxyl group in the B-ring) have different biological activities but, both possess high antioxidant abilities. Quercetin during the antioxidative action, is converted into an oxidized products (o-semiquinone and o-quinone), and subsequently glutathionyl adducts may be formed or SH-enzyme can be inhibited. We have tried to see whether inhibition of glutathione reductase (GR) can be influenced by preincubation of enzyme with NADPH (a creation of reduced form of enzyme, GRH(2)) and whether diaphorase activity of the enzyme is decreased by these flavonoids. The results confirmed that quercetin inhibits GRH(2) and inhibition is reduced by addition of EDTA or N-acetylcysteine. Both of flavonoids have no effect on diaphorase activity of glutathione reductase and this enzyme could increase the production of free radicals by catalysis of reduction of o-quinone during action of quercetin in vivo.
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PMID:The effect of quercetin and galangin on glutathione reductase. 1660 19

Addition of U(VI) (uranyl acetate) to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential, and lysosomal membrane rupture before hepatocyte lysis occurred. Cytotoxicity was prevented by ROS scavengers, antioxidants, and glutamine (ATP generator). Hepatocyte dichlorofluorescein oxidation was inhibited by mannitol (a hydroxyl radical scavenger) or butylated hydroxyanisole and butylated hydroxytoluene (antioxidants). Glutathione depleted hepatocytes were resistant to U(VI) toxicity and much less dichlorofluorescein oxidation occurred. Reduction of U(VI) by glutathione or cysteine in vitro was also accompanied by oxygen uptake and was inhibited by Ca(II) (a U(IV) or U(VI) reduction inhibitor). U(VI)-induced cytotoxicity and ROS formation was also inhibited by Ca(II), which suggests that U(IV) and U(IV) GSH mediate ROS formation in isolated hepatocytes. The U(VI) reductive mechanism required for toxicity has not been investigated. Cytotoxicity was also prevented by cytochrome P450 inhibitors, particularly CYP 2E1 inhibitors, but not inhibitors of DT diaphorase or glutathione reductase. This suggests that P450 reductase and reduced cytochrome P450 contributes to U(VI) reduction to U(IV). In conclusion, U(VI) cytotoxicity is associated with mitochondrial/lysosomal toxicity by the reduced biological metabolites and ROS.
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PMID:A search for cellular and molecular mechanisms involved in depleted uranium (DU) toxicity. 1684 14

The modulatory efficacy of capsaicin on lung mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, key citric acid cycle enzymes and respiratory chain enzymes during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice was studied. Elevations in mitochondrial LPO along with decrements in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and vitamin A), citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (alpha-KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and respiratory chain enzymes (NADH dehydrogenase and Cytochrome c oxidase) were observed in B(a)P (50mg/kg body weight) administered animals. CAP (10mg/kg body weight) pretreatment decreased lung mitochondrial LPO and augmented the activities of enzymic, non-enzymic antioxidants, citric acid cycle enzymes and respiratory chain enzymes to near normalcy revealing its chemoprotective function during B(a)P induced lung cancer.
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PMID:Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer. 1802 35

The mechanism of free radical production by complex I deficiency is ill-defined, although it is of significant contemporary interest. This study studied the ROS production and antioxidant defenses in children with mitochondrial NADH dehydrogenase deficiency. ROS production has remained significantly elevated in patients compared to controls. The expression of all antioxidant enzymes significantly increased at mRNA level. However, the enzyme activities did not correlate with high mRNA or protein expression. Only the activity of superoxide dismutase (SOD) was found to correlate with higher mRNA expression in patient derived cell lines. The activities of the enzymes such as glutathione peroxidase (GPx), Catalase (CAT) and glutathione-S-transferase (GST) were significantly reduced in patients (p<0.05 or p<0.01). Glutathione reductase (GR) activity and intracellular glutathione (GSH) levels were not changed. Decreased enzyme activities could be due to post-translational or oxidative modification of ROS scavenging enzymes. The information on the status of ROS and marking the alteration of ROS scavenging enzymes in peripheral lymphocytes or lymphoblast cell lines will provide a better way to design antioxidant therapies for such disorders.
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PMID:Analysis of reactive oxygen species and antioxidant defenses in complex I deficient patients revealed a specific increase in superoxide dismutase activity. 1855 9

Naringenin is a flavanone that is believed to have many biological actions, including as an anti-oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl) in rats. Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S-NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks. In Group II rats in which gastric cancer was inducted with MNNG and S-NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochrome b(5) and NADPH cytochrome c reductase, with concomitant decreases in the activity of the phase II enzymes glutathione S-transferase and UDP-glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels. These results indicate that naringenin has a chemopreventive action against MNNG-induced gastric carcinoma in experimental rats.
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PMID:Modulatory effect of naringenin on N-methyl-N'-nitro-N-nitrosoguanidine- and saturated sodium chloride-induced gastric carcinogenesis in male Wistar rats. 1856 95

The present study investigates the effect of aspartate and glutamate on mitochondrial function during myocardial infarction (MI) in wistar rats. Male albino wistar rats were pretreated with aspartate [100 mg(kgbody weight)(-1) day(-1)] or glutamate [100 mg(kg body weight)(-1) day(-1)] intraperitoneally for a period of 7 days. Following amino acid treatment, MI was induced in rats by subcutaneous injection of isoproterenol [200 mg(kg body weight)(-1) day(-1)] for 2 days at an interval of 24 h. Isoproterenol (ISO) induction resulting in significant (P<0.05) increase in the levels of cardiac mitochondrial lipid peroxidation with a decrease in reduced glutathione level. The activities of glutathione peroxidase and glutathione reductase were significantly (P<0.05) decreased by ISO. ISO-induction also caused significant (P<0.05) decrease in the activities of mitochondrial tricarboxylic acid cycle enzymes (malate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase) and respiratory chain enzymes (NADH dehydrogenase and cytochrome-c-oxidase). ISO significantly (P<0.05) reduced the cytochrome contents, ATP production, ADP/O ratio and oxidation of succinate in state 3/state 4 whereas significantly (P<0.05) increased NADH oxidation. Pretreatment with aspartate or glutamate significantly (P<0.05) reduced the alterations induced by ISO and maintained normal mitochondrial function. The present findings reveal the protective effect of aspartate and glutamate on cardiac mitochondrial function in myocardial infarction-induced rats.
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PMID:Protective effect of aspartate and glutamate on cardiac mitochondrial function during myocardial infarction in experimental rats. 1878 22

One of the key functions of nitric oxide (NO) in human is to dilate blood vessels. We tested glycerol trinitrate (GTN) and other well-known NO donors together with those bearing a >C=N-OH group for possible conversion to NO (or nitrites, respectively) by diaphorase (DP) and lipoamide dehydrogenase (LAD). Both, DP and LAD were unable to convert formamidoxime (FAM), acetone oxime (AC), acetohydroxamic acid (AHA) and Nomega-hydroxy-L-arginine (L-NOHA). On the other hand, we observed good conversion of GTN without the requirement of superoxide anion. However, superoxide anion participated to a varying extent in the conversion of other donors (formaldoxime (FAL), acetaldoxime (AO), nitroprusside (NP), S-nitrosoglutathione (SNOG), S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine (HA)). All DP- and LAD-mediated reactions were inhibited by diphenyleneiodonium chloride (DPI), (an inhibitor of flavine enzymes), in a concentration-dependent manner. For these inhibition reactions we determined Ki and IC50 values. In addition, we found that conversion of SNOG was significantly accelerated by glutathione reductase (GTR). Like with DP, 2-phenyl- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) was reduced also by LAD and thioredoxin reductase (TRR). In summary, we found that LAD significantly accelerates the conversion of a defined subset of NO donors to NO, especially GTN, and eliminates the NO scavenging effect of PTIO.
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PMID:Lipoamide dehydrogenase and diaphorase catalyzed conversion of some NO donors to NO and reduction of NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). 2009 61

Consumption of fruits and vegetables has been associated with a low incidence of cardiovascular and other chronic diseases. The present study was aimed at evaluating the protective effects of fresh apple extract (AE) on human umbilical vein endothelial cells (HUVEC) exposed to cytotoxic glycated protein (GFBS)/iron (FeCl(3)) chelate. The experimental design comprised 10 groups with 5 flasks in each group. Group I was treated with 15% foetal bovine serum (FBS). Groups II, III and IV were treated with GFBS (70 microM), FBS + FeCl(3) (20 microM), and GFBS + FeCl(3), respectively. The other six groups were as follows: Group V, GFBS + AE (100 microg); Group VI, FBS + FeCl(3) + AE (100 microg); Group VII, GFBS + FeCl(3) + AE (100 microg); Group VIII, GFBS + AE (250 microg); Group IX, FBS + FeCl(3) + AE (250 microg); and Group X, GFBS + FeCl(3) + AE (250 microg). After 24 h incubation, cells were collected from all the experimental groups and assessed for lipid peroxidation (LPO) and activities of the antioxidant enzymes cytochrome c reductase and glutathione S-transferase (GST). HUVEC incubated with glycated protein (GFBS) either alone or combined with iron chelate showed a significant (p < 0.001) elevation of LPO accompanied by depletion of superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to increased microsomal cytochrome c reductase and decreased GST activities. Treatment of GFBS- or GFBS + FeCl(3)-exposed HUVEC with AE at 100 or 250 microg significantly decreased the level of LPO and returned the levels of antioxidants cytochrome c reductase and GST to near normal in a dose-dependent manner. The extracts recovered viability of HUVEC damaged by GFBS-iron treatment in a concentration-dependent manner. These findings suggest a protective effect of AE on HUVEC against glycated protein/iron chelate-induced toxicity, which suggests that AE could exert a beneficial effect by preventing diabetic angiopathies.
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PMID:Effect of fresh apple extract on glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells in vitro. 2040 91

Bisphenol A (BPA) is a monomer of polycarbonate plastic used to manufacture plastic baby bottles and lining of food cans. It has endocrine-disrupting potential and exerts both toxic and estrogenic effects on mammalian cells. We studied BPA-induced perturbation of mitochondrial marker enzymes in testes of Swiss albino mice and its amelioration by melatonin. Mice exposed to standardized dose of BPA (10 mg/kg body weight) orally for 14 days showed decrease in activities of marker mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. Besides, it also affected activities of antioxidant enzymes such as superoxide dismutase, glutathione reductase and glutathione peroxidase. BPA also caused lipid peroxidation (LPO) and decrease in reduced glutathione (GSH) content of mitochondria. Concomitant melatonin administration (10 mg/kg body weight; intraperitoneally for 14 days) lowered mitochondrial lipid peroxidation. It also restored the activity of mitochondrial marker enzymes and ameliorated decreased enzymatic and non-enzymatic antioxidants of mitochondria. These results demonstrate that melatonin has a potential role in ameliorating BPA-induced mitochondrial toxicity and the protection is due to its antioxidant property or by the direct free radical scavenging activity.
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PMID:Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse. 2184 Mar 68


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