ascorbic-acid has been researched along with divicine* in 8 studies
8 other study(ies) available for ascorbic-acid and divicine
Article | Year |
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The role of plasma in oxidative haemolysis.
Topics: Ascorbic Acid; Carbon Monoxide; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Oxidation-Reduction; Peroxides; Plasma; Pyrimidinones; tert-Butylhydroperoxide | 1986 |
Effect of the redox state of the red blood cell components on the inactivation of glutathione peroxidase by divicine.
The redox state of red blood cell components was found to have profound effects on the specific inactivation of erythrocyte glutathione (GSH) peroxidase by divicine, a hydroquinone imine molecule of fava beans likely to be responsible, through redox cycling, of the oxidative damage of red blood cells ultimately resulting in the hemolysis of favism. Oxidation of hemoglobin is a necessary step for the inactivation to take place, apparently as a H2O2-MetHb adduct. On the other hand, the presence of either reduced NADP or glutathione enhances the inactivating effect although NADPH inhibits the oxidation of hemoglobin, and this suggests a catalytic role for MetHb in the inactivation process. Topics: Ascorbic Acid; Catalase; Cell-Free System; Erythrocytes; Glutathione; Glutathione Peroxidase; Humans; In Vitro Techniques; Methemoglobin; NADP; Oxidation-Reduction; Pyrimidinones | 1986 |
Mechanism of action of divicine in a cell-free system and in glucose-6-phosphate dehydrogenase-deficient red cells.
Favism is an acute hemolysis occurring in glucose-6-phosphate dehydrogenase (G6PD)-deficient (Mediterranean variant) individuals after intake of fava beans. Divicine (D), 2,6-diamino-4,5-dihydroxypyrimidine, is present in high amounts in the beans, and is suspected to play a role in hemolysis. Its mechanism of action was studied in a cell-free system and in G6PD (Mediterranean variant)-deficient red cells (RBC). Upon hydrolysis of the inactive beta-glucoside vicine, reduced divicine is formed. Oxygen acts as a one- or two-electron acceptor; superoxide anion and hydrogen peroxide are formed, respectively, together with the semiquinoid free-radical form of D. This free radical gives an electron spin resonance (ESR) signal, which is similar to that of the alloxan free radical. Added reduced glutathione (GSH) is rapidly oxidized with a stoichiometry of one to one, and the ESR signal is abolished. Additional GSH is oxidized by hydrogen peroxide and by a slow redox cycle which continuously regenerates oxidized D. The fast-direct and the slow-indirect oxidation result in nonstoichiometric oxidation of GSH. D added to G6PD-deficient RBC rapidly oxidizes GSH with an end point kinetics and a stoichiometry of one to one. Hydrogen peroxide and superoxide anion are scavenged in the RBC and no redox cycling is taking place. No GSH is regenerated even after long incubation periods. After the primary event, i.e., oxidation of GSH and--SH groups, a number of metabolic, rheologic, and membrane modifications, together with increased erythrophagocytosis take place in G6PD-deficient, D-treated RBC only.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Ascorbic Acid; Cell-Free System; Cytochrome c Group; Erythrocytes; Favism; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Hemolysis; Humans; Hydrogen Peroxide; In Vitro Techniques; Kinetics; Male; Oxidation-Reduction; Pyrimidinones; Superoxides | 1984 |
Transition metals mediate enzymatic inactivation caused by favism-inducing agents.
Enzymatic activity of purified or membrane-bound acetylcholine esterase was lost when incubated aerobically in the presence of both favism-inducing agent (isouramil or divicine) and copper ions. The requirement for oxygen could be substituted by hydrogen peroxide. Chelating agents provided total protection to the proteins. The suggested mechanism of enzymatic inactivation is analogous to that suggested earlier for the effects of superoxide and ascorbate, and involves the site-specific formation of hydroxyl radicals in the metal-mediated Haber-Weiss reaction. These findings may be relevant to the understanding of the pathogenesis of favism. Topics: Ascorbic Acid; Barbiturates; Cholinesterase Inhibitors; Copper; Electron Spin Resonance Spectroscopy; Favism; Humans; In Vitro Techniques; Oxidation-Reduction; Pyrimidinones | 1984 |
Mediterranean glucose 6-phosphate dehydrogenase (G6PD) deficiency--near normal decay of the mutant enzyme protein in circulating erythrocytes.
Complete removal of leucocytes and platelets from erythrocytes and the development of a sensitized procedure for the assay of G6PD activity allowed the biochemical mechanisms of the Mediterranean variety of G6PD deficiency to be re-evaluated. Activity in the young erythrocytes from 9 G6PD-deficient subjects averaged 0.1% of the levels observed in the corresponding erythrocyte fraction from normal individuals: moreover, the decline of activity during aging of the G6PD-deficient erythrocytes was comparable with that observed for the normal enzyme. Mutant G6PD purified from granulocytes of a G6PD-deficient subject and entrapped within the corresponding erythrocytes was remarkably stable. Exposure of native erythrocytes to an oxidative stress (divicine plus ascorbate) resulted in a decrease of G6PD activity that was significantly more rapid and extensive in control than in G6PD-deficient cells. These results seem to exclude enhanced intracellular breakdown of the mutant protein within the circulating erythrocytes. Topics: Ascorbic Acid; Erythrocyte Aging; Erythrocytes; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Male; Mediterranean Islands; Mutation; Pyrimidinones | 1984 |
Favism: a hemolytic disease associated with increased superoxide dismutase and decreased glutathione peroxidase activities in red blood cells.
Red blood cells of favism patients with acute hemolytic crisis have markedly more superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and less glutathione peroxidase (glutathione:hydrogenperoxide oxidoreductase, EC 1.11.1.9) than either normal controls, glucose-6-phosphate dehydrogenase-deficient subjects or favism patients outside hemolytic crisis. This altered value of the two enzyme activities is not due to increased reticulocyte content of blood. The electrophoretic triplet pattern of superoxide dismutase is also changed, with significant increase of the most positively charged band. Similar modifications of the two enzyme activities are observed after treatment of normal red blood cells with high concentrations of divicine and ascorbate, which are redox compounds that are contained in fava seeds. This treatment produces no hemolysis, but leads to hemolysis if the treated cells are resuspended in the homologous plasma. These results suggest a possible role of active oxygen species in the development of favism. Topics: Ascorbic Acid; Electrophoresis, Polyacrylamide Gel; Erythrocyte Aging; Erythrocytes; Favism; Glutathione Peroxidase; Hemolysis; Humans; Oxidation-Reduction; Pyrimidinones; Reticulocytes; Superoxide Dismutase | 1984 |
Oxidant damage of normal and glucose 6-phosphate dehydrogenase (G6PD)-deficient red blood cells is enhanced by iron-EDTA complex.
A combination of divicine (an aglycone from the fava bean beta-glucoside vicine) and ascorbate results in a marked production of ethylene from methional, as a probable indication of OH radical formation. Addition of iron-EDTA to this oxidising system enhances the ethylene production significantly. The enhancing effect of iron-EDTA is also observed when both normal and Glucose 6-phosphate dehydrogenase (G6PD)-deficient red cells are exposed to the divicine-ascorbate system. Moreover, iron-EDTA magnifies other consequences of oxidant damage afforded by divicine-ascorbate or by ascorbate alone on the target red cells, such as depletion of reduced glutathione, formation of methemoglobin, stimulation of hexose monophosphate shunt activity and lipid peroxidation. Although the biochemical changes induced by this oxidative system are not remarkably different in normal and in G6PD-deficient red cells, the extra-damaging effect of chelated iron might be important in the mechanism of hemolysis. Topics: Ascorbic Acid; Catalase; Edetic Acid; Erythrocytes; Ferric Compounds; Free Radicals; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Humans; Hydroxides; Hydroxyl Radical; Iron; Male; Oxygen; Pyrimidinones | 1983 |
Effect of divicine and isouramil on red cell metabolism in normal and G6PD-deficient (Mediterranean variant) subjects. Possible role in the genesis of favism.
Fava beans contain high amounts (up to 6.7 g/100 g dry weight) vicine and convicine. Their active aglycones divicine and isouramil have equivalent metabolic effects. They rapidly oxidize GSH to GSSG in normal and G6PD-deficient red cells. No regeneration of GSH occurs in deficient cells. The stoichiometry of the divicine oxidation of GSH is 1:1. Ascorbic acid is quickly oxidized by isouramil in both normal and deficient cells but regenerates only in normal cells. Isouramil oxidizes NADH at a much lesser extent than NADPH. Glycolysis is activated at the glyceraldehyde 3-phosphate dehydrogenase step. Divicine strongly stimulates hexone monophosphate shunt only in normal red cells. Divicine alone or associated with ascorbic acid has almost no effect in deficient red cells. Malonyl dialdehyde production is slight and virtually the same in normal and deficient cells treated with 5 mM isouramil. Large polypeptide aggregates are formed after 12 and 24 hours incubation with 1 mM divicine in deficient cells only. Divicine (0.25 mM) markedly decreases the filterability of deficient cells. The results are consistent with a causal role of divicine/isouramil in the genesis of the hemolytic crisis occurring in G6PD-deficient subjects after fava bean ingestion. Topics: Ascorbic Acid; Barbiturates; Erythrocytes; Favism; Glucosephosphate Dehydrogenase Deficiency; Glucosides; Glutathione; Humans; Kinetics; Pyrimidinones; Reference Values; Species Specificity; Toxins, Biological; Uracil; Uridine | 1981 |