Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes the development of a modified electrode for the electrocatalytic oxidation of beta-nicotinamide adenine dinucleotide (beta-NADH) and beta-nicotinamide adenine dinucleotide phosphate (beta-NADPH) using electropolymerised 3,4-dihydroxybenzaldehyde (3,4-DHB). Two voltammetric biosensors using enzyme-immobilised membranes were constructed for the determination of formic acid and glucose-6-phosphate (G6P), respectively. The formic acid biosensor based on the combination of formate dehydrogenase (FDH)-modified membrane with 3,4-DHB-coated glassy carbon electrode is one to two orders more sensitive (LOD, 5.0x10(-5) M) than previously reported electrochemical biosensors. Similarly, lower detection limit (4.0x10(-5) M) for the measurement of G6P was achieved using glucose-6-phosphate dehydrogenase (G6PDH) in the presence of beta-NADP(+). The interference of uric acid and ascorbate was minimised by incorporating an additional membrane modified with uricase and ascorbate oxidase, respectively. The biosensing scheme developed in this study can be adopted universally with a number of dehydrogenases for the detection of different substrates.
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PMID:Voltammetric biosensors for the determination of formate and glucose-6-phosphate based on the measurement of dehydrogenase-generated NADH and NADPH. 1134

It has been proposed that GLUT1, a membrane protein that transports hexoses and the oxidized form of vitamin C, dehydroascorbic acid, is also a transporter of nicotinamide (Sofue, M., Yoshimura, Y., Nishida, M., and Kawada, J. (1992) Biochem. J. 288, 669-674). To ascertain this, we studied the transport of 2-deoxy-D-glucose, 3-O-methyl-D-glucose, and nicotinamide in human erythrocytes and right-side-out and inside-out erythrocyte membrane vesicles. The transport of nicotinamide was saturable, with a K(M) for influx and efflux of 6.1 and 6.2 mM, respectively. We found that transport of the hexoses was not competed by nicotinamide in both the erythrocytes and the erythrocyte vesicles. Likewise, the transport of nicotinamide was not affected by hexoses or by inhibitors of glucose transport such as cytochalasin B, genistein, and myricetin. On the other hand, nicotinamide blocked the binding of cytochalasin B to human erythrocyte membranes but did so in a noncompetitive manner. Using GLUT1-transfected CHO cells, we demonstrated that increased expression of GLUT1 was paralleled by a corresponding increase in hexose transport but that there were no changes in nicotinamide transport. Moreover, nicotinamide failed to affect the transport of hexoses in both control and GLUT1-transfected CHO cells. Therefore, our results indicates that GLUT1 does not transport nicotinamide, and we propose instead the existence of other systems for the translocation of nicotinamide across cell membranes.
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PMID:Nicotinamide is not a substrate of the facilitative hexose transporter GLUT1. 1206 99

Alpha-lipoic acid, which becomes a powerful antioxidant in its reduced form, has been suggested as a dietary supplement to treat diseases associated with excessive oxidant stress. Because the vascular endothelium is dysfunctional in many of these conditions, we studied the uptake, reduction, and antioxidant effects of alpha-lipoic acid in cultured human endothelial cells (EA.hy926). Using a new assay for dihydrolipoic acid, we found that EA.hy926 cells rapidly take up and reduce alpha-lipoic acid to dihydrolipoic acid, most of which is released into the incubation medium. Nonetheless, the cells maintain dihydrolipoic acid following overnight culture, probably by recycling it from alpha-lipoic acid. Acute reduction of alpha-lipoic acid activates the pentose phosphate cycle and consumes nicotinamide adenine dinucleotide phosphate (NADPH). Lysates of EA.hy926 cells reduce alpha-lipoic acid using both NADPH and nicotinamide adenine dinucleotide (NADH) as electron donors, although NADPH-dependent reduction is about twice that due to NADH. NADPH-dependent alpha-lipoic acid reduction is mostly due to thioredoxin reductase. Pre-incubation of cells with alpha-lipoic acid increases their capacity to reduce extracellular ferricyanide, to recycle intracellular dehydroascorbic acid to ascorbate, to decrease reactive oxygen species generated by redox cycling of menadione, and to generate nitric oxide. These results show that alpha-lipoic acid enhances both the antioxidant defenses and the function of endothelial cells.
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PMID:Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. 1208 86

Ascorbic acid (AA) and its derivatives participate in vitro in oxidative-reductive reactions both as antioxidants and as prooxidants. The physiological relevance of these prooxidant effects of AA and its derivatives remains unclear. There is little evidence that AA can initiate formation of reactive oxygen species (ROS) or lipid peroxidation in cells or tissue. In order to examine the effect of AA and its derivative palmitoyl ascorbate on in situ intracellular ROS production and lipid peroxidation, 2('),7(')-dichlorofluorescin diacetate (DCFH-DA) and cis-parinaric acid were used as fluorescent probes in cultural neonatal foreskin fibroblasts. The results demonstrated that the effect of AA depended on the in vitro growth conditions. AA induced augmentation of the intracellular ROS concentration in newly plated (24 hours) cells. However, in cells cultured for 72 hours, AA had a different effect: it moderately reduced intracellular ROS concentration but stimulated lipid peroxidation in the cytoplasmic membrane. Palmitoyl ascorbate demonstrated significant inhibition of intracellular DCFH-DA oxidation presumably caused by inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
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PMID:Effect of Ascorbic Acid and Its Hydrophobic Derivative Palmitoyl Ascorbate on the Redox State of Primary Human Fibroblasts. 1263 19

From experiments in vitro (E. coli bacteria AB 1157) it was established that the cytostatic activity of nicotinamide (vitamin B3) in aqueous, aerated media (pH = 7.4) under irradiation with gamma-rays can be strongly enhanced in the presence of antioxidant vitamins. Whereas the addition of beta-carotene (beta-car) increases nicotinamide activity by a factor of 1.7, vitamin E (vit.E) of 2.16 and vitamin C (vit.C) of 2.3, in the presence of all three vitamins (beta-car, vit.E and C) a four times enhancement is observed. This ability of the vitamins to affect so strongly the cytostatic properties of nicotinamide is of interest for the radiation therapy of patients.
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PMID:Effect of vitamin C, E-acetate and beta-carotene on the cytostatic activity of nicotinamide (vitamin B3). 1279 80

Methaemoglobin is formed by oxidation of ferrous (FeII) haem to the ferric (FeIII) state and the mechanisms by which this occurs are complex. Most cases are due to one of three processes. Firstly, direct oxidation of ferrohaemoglobin, which involves the transfer of electrons from ferrous haem to the oxidising compound. This mechanism proceeds most readily in the absence of oxygen. Secondly, indirect oxidation, a process of co-oxidation which requires haemoglobin-bound oxygen and is involved, for example, in nitrite-induced methaemoglobinaemia. Thirdly, biotransformation of a chemical to an active intermediate that initiates methaemoglobin formation by a variety of mechanisms. This is the means by which most aromatic compounds, such as amino- and nitro-derivatives of benzene, produce methaemoglobin. Methaemoglobinaemia is an uncommon occupational occurrence. Aromatic compounds are responsible for most cases, their lipophilic nature and volatility facilitating absorption during dermal and inhalational exposure, the principal routes implicated in the workplace. Methaemoglobinaemia presents clinically with symptoms and signs of tissue hypoxia. Concentrations around 80% are life-threatening. Features of toxicity may develop over hours or even days when exposure, whether by inhalation or repeated skin contact, is to relatively low concentrations of inducing chemical(s). Not all features observed in patients with methaemoglobinaemia are due to methaemoglobin formation. For example, the intravascular haemolysis caused by oxidising chemicals such as chlorates poses more risk to life than the methaemoglobinaemia that such chemicals induce. If an occupational history is taken, the diagnosis of methaemoglobinaemia should be relatively straightforward. In addition, two clinical observations may help: firstly, the victim is often less unwell than one would expect from the severity of 'cyanosis' and, secondly, the 'cyanosis' is unresponsive to oxygen therapy. Pulse oximetry is unreliable in the presence of methaemoglobinaemia. Arterial blood gas analysis is mandatory in severe poisoning and reveals normal partial pressures of oxygen (pO2) and carbon dioxide (pCO2,), a normal 'calculated' haemoglobin oxygen saturation, an increased methaemoglobin concentration and possibly a metabolic acidosis. Following decontamination, high-flow oxygen should be given to maximise oxygen carriage by remaining ferrous haem. No controlled trial of the efficacy of methylene blue has been performed but clinical experience suggests that methylene blue can increase the rate of methaemoglobin conversion to haemoglobin some 6-fold. Patients with features and/or methaemoglobin concentrations of 30-50%, should be administered methylene blue 1-2 mg/kg/bodyweight intravenously (the dose depending on the severity of the features), whereas those with methaemoglobin concentrations exceeding 50% should be given methylene blue 2 mg/kg intravenously. Symptomatic improvement usually occurs within 30 minutes and a second dose of methylene blue will be required in only very severe cases or if there is evidence of ongoing methaemoglobin formation. Methylene blue is less effective or ineffective in the presence of glucose-6-phosphate dehydrogenase deficiency since its antidotal action is dependent on nicotinamide-adenine dinucleotide phosphate (NADP+). In addition, methylene blue is most effective in intact erythrocytes; efficacy is reduced in the presence of haemolysis. Moreover, in the presence of haemolysis, high dose methylene blue (20-30 mg/kg) can itself initiate methaemoglobin formation. Supplemental antioxidants such as ascorbic acid (vitamin C), N-acetylcysteine and tocopherol (vitamin E) have been used as adjuvants or alternatives to methylene blue with no confirmed benefit. Exchange transfusion may have a role in the management of severe haemolysis or in G-6-P-D deficiency associated with life-threatening methaemoglobinaemia where methylene blue is relatively contraindicated.
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PMID:Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. 1457 44

A simple and reliable method for the preparation of biological samples for the evaluation of biochemical parameters representative of the redox and energy states, such as glutathione (GSH), oxidized glutathione (GSSG), oxidized nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide (NADH), oxidized nicotinamide adenine dinucleotide phosphate (NADP+), reduced nicotinamide adenine dinucleotide phosphate (NADPH), coenzyme A (CoASH), oxidized CoASH, ascorbate, malondialdehyde, oxypurines, nucleosides, and energy metabolites, is presented. Fast deproteinization under nonoxidizing conditions is obtained by tissue homogenization in ice-cold, nitrogen-saturated CH3CN + 10 mM KH2PO4 (3:1; v:v), pH 7.40. After sample centrifugation to pellet precipitated proteins, organic solvent removal is performed on clear supernatants by three washings with large volumes of high-performance liquid chromatography (HPLC)-grade chloroform. The remaining aqueous phase, free of solvent and any lipid-soluble substances that may interfere with the further metabolite analysis, is used for the simultaneous ion-pairing HPLC determination of 39 compounds by means of a Kromasil C-18, 250 x 4.6-mm, 5-microm-particle-size column with tetrabutylammonium hydroxide as the pairing reagent. Results obtained by using the present method to prepare different rat tissue extracts demonstrate that it is possible to perform a single tissue preparation only for monitoring, in the same sample, compounds representative of the redox state (through the direct determination of GSH, GSSG, NAD+, NADH, NADP+, NADPH, CoASH, and oxidized CoASH) and of the cell energy state (by the analysis of oxypurines, nucleosides, and energy metabolites). Applicability of this sample processing procedure to quantify variations of the aforementioned compounds under pathological conditions was effected in rats subjected to moderate closed-head trauma.
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PMID:Single-sample preparation for simultaneous cellular redox and energy state determination. 1470 80

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) that exhibits analgesic, antipyretic and anti-inflammatory activities. It is practically insoluble in water. The effect of various hydrotropes such as nicotinamide, sodium ascorbate, sodium benzoate, sodium salicylate and piperazine on the solubility of nimesulide was investigated. The solubility enhancement of nimesulide by the hydrotropes was observed in decreasing order as piperazine > sodium ascorbate > sodium salicylate > sodium benzoate > nicotinamide. In order to elucidate the probable mechanism of solubilization, various solution properties of hydrotropes such as viscosity, specific gravity, surface tension, refractive index, specific conductance of hydrotropic solutions were studied at 25 +/- 2 degrees C on the basis of earlier studies. The hydrotropic solubilization of nimesulide at lower hydrotrope concentration may be attributed to weak ionic interactions while that at higher hydrotrope concentration may be due to molecular aggregation. Parenteral formulations using piperazine as a hydrotrope were developed and studied for physical and chemical stability.
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PMID:Hydrotropic solubilization of nimesulide for parenteral administration. 1507 91

The antioxidant effects of natural vitamin B(6) compounds on Schizosaccharomyces pombe cells treated with menadione sodium bisulfite (water-soluble menadione and a generator of superoxide, MSB) and the mechanism underlying the function were examined with the yeast cells treated with pyridoxal 5'-phosphate. Vitamin B(6) compounds showed no ex vivo reactivity toward MBS at pH 5.5 or 7.0. The yeast cells showed no growth in the medium containing 1.0 mM MSB. The coexistence of 1.0 mM of each vitamin B(6) compound supported the growth of the yeast cells. The efficacy order was pyridoxal 5'-phosphate>/=pyridoxamine 5'-phosphate>pyridoxamine>pyridoxal>/=pyridoxine. The first three compounds showed higher antioxidant activity than vitamin C did. Pyridoxal 5'-phosphate prevented the reduction of the glutathione content in the MSB-treated cells and, in turn, suppressed the increases in peroxide and thiobarbituric acid reactive substances in the yeast cells and increased the viability of the yeast cells under oxidative stress. The antioxidant function of pyridoxal 5'-phosphate was not dependent on the phosphorelay pathway, which finally triggers the expression of the catalase gene.
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PMID:Vitamin B6 compounds prevent the death of yeast cells due to menadione, a reactive oxygen generator. 1571 32

Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.
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PMID:The role of antioxidant micronutrients in the prevention of diabetic complications. 1574 12


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