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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to establish a possible relationship between hemolytic and peroxidant activities of copper ions, lipid peroxidation was studied in plasma and whole blood incubated for 24 h with different concentrations of copper. The lipid peroxidation was investigated by the determination of thiobarbituric acid-reactive species, conjugated dienes and fluorescent lipid chromophores. The copper-induced lipoperoxidation was clearly demonstrated in plasma incubated with high concentrations of copper (12.10(-4) and 20.10(-4) M); in whole blood, all the lipoperoxidation products were increased in the plasma, while the fluorescent lipid chromophores remained unchanged in red cells. With a copper concentration similar to that found in acute copper intoxication (4.10(-4) M) no lipoperoxidation was observed and yet hemolysis occurred, reduced glutathione (GSH) decreased dramatically and methemoglobin (MetHb) increased. From these results, we assume that, despite its prooxidant activity and its capacity to produce lipoperoxidation, it has not been proven that copper ions at pathophysiological concentrations induce hemolysis by an oxidative mechanism.
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PMID:Copper-induced lipid peroxidation and hemolysis in whole blood: evidence for a lack of correlation. 342 89

Depletion of selenium from rats for 8 weeks decreased blood glutathione peroxidase activity to 5.7% of that in selenium-supplemented (0.5 ppm selenium as Na2SeO3) rats. Aniline (60 mg/kg, i.p.) resulted in no significant difference in methemoglobin and blood reduced glutathione (GSH) levels between Se-deficient and Se-supplemented rats. A lowered aniline dose (36 mg/kg, i.p.) also resulted in no difference in methemoglobin levels. The selenium-deficient rat was able to reduce methemoglobin induced by aniline as efficiently as the selenium-sufficient rat.
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PMID:Dietary selenium and aniline-induced methemoglobinemia in rats. 400 49

We have reported previously that the antimicrobial nitrofurantoin stimulates superoxide production and methemoglobin formation from HbO2 as an isolated hemeprotein and in hemolysates [M. Dershwitz and R. F. Novak, J. biol. Chem. 257, 75 (1982); M. Dershwitz and R. F. Novak, J. Pharmac. exp. Ther. 222, 430 (1982)]. The production of hydrogen peroxide and methemoglobin by nitrofurantoin has been determined in normal erythrocytes in vitro. Hydrogen peroxide production increased 5-fold during a 20-hr incubation in the presence of 840 microM nitrofurantoin, while methemoglobin content increased to over 20% of the total hemoglobin concentration of the cells. Consequent metabolic and morphologic alterations also occurred. Concomitant with nitrofurantoin-stimulated hydrogen peroxide production were time- and concentration-dependent decreases in cellular levels of GSH and ATP, as well as alterations in red cell morphology. Significant differences in GSH and ATP levels between control and nitrofurantoin-treated erythrocytes occurred after 12 hr and proceeded maximally from 18 to 21 hr. After a 21-hr incubation, 840 microM nitrofurantoin caused the cellular GSH and ATP levels to fall 65 and 75%, respectively, while controls exhibited only 29 and 43% decreases in ATP and GSH levels, respectively. Studies on the concentration dependence of such decreases demonstrated that the EC50 values for depletion of GSH and ATP were similar in blood obtained from an individual donor. The EC50 values varied from approximately 10 microM to 100 microM among the various donors whose blood was studied. Incubation of normal red cells with nitrofurantoin also resulted in an increased conversion of red cells to echinocytes as observed by scanning electron microscopy. These metabolic effects, coupled with increased oxidative stress via hydrogen peroxide generation, lend support to the mechanism for nitrofurantoin-induced hemolysis in erythrocytes compromised by certain enzyme deficiencies which result in low basal levels of GSH or diminished rates of GSH synthesis.
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PMID:Metabolic and morphologic effects of the antimicrobial agent nitrofurantoin on human erythrocytes in vitro. 400 12

Reduced divicine (2,6-diamino-4,5-dihydroxypyrimidine), an aglycone implicated in the pathogenesis of favism, reduces methemoglobin efficiently in intact erythrocytes and in hemolysates. Oxidized divicine produces the same effect when glucose or an NADPH-generating system is added to intact erythrocytes or to hemolysates. Although NADPH, NADH, and GSH have no direct methemoglobin-reducing activity in vitro, they convert oxidized divicine to the reduced hydroquinone species, which is responsible for the electron transfer to methemoglobin. Reduction of methemoglobin is optimally observed under nitrogen since, in the presence of oxygen, reduced divicine undergoes autoxidation. Several lines of evidence rule out the reduction of methemoglobin by divicine through an enzyme-catalyzed process, although it is certainly sustained by the hexose monophosphate shunt activity of erythrocytes through the generation of both NADPH and GSH. Thus, the strong enhancing effect that glucose produces on the divicine-dependent methemoglobin reduction within intact normal erythrocytes is completely absent in erythrocytes from glucose-6-phosphate dehydrogenase-deficient subjects. This distinctive behavior might account for the enhanced methemoglobin levels that are found both in vitro in glucose-6-phosphate dehydrogenase-deficient erythrocytes exposed to divicine and in vivo as a typical feature of the acute hemolytic crisis of favic patients.
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PMID:Hexose monophosphate shunt-stimulated reduction of methemoglobin by divicine. 406 95

Glyceryl trinitrate specifically required cysteine, whereas NaNO2 at concentrations less than 10 mM required one of several thiols or ascorbate, to activate soluble guanylate cyclase from bovine coronary artery. However, guanylate cyclase activation by nitroprusside or nitric oxide did not require the addition of thiols or ascorbate. Whereas various thiols enhanced activation by nitroprusside, none of the thiols tested enhanced activation by nitric oxide. S-Nitrosocysteine, which is formed when cysteine reacts with either NO-2 or nitric oxide, was a potent activator of guanylate cyclase. Similarly, micromolar concentrations of the S-nitroso derivatives of penicillamine, GSH and dithiothreitol, prepared by reacting the thiol with nitric oxide, activated guanylate cyclase. Guanylate cyclase activation by S-nitrosothiols resembled that by nitric oxide and nitroprusside in that activation was inhibited by methemoglobin, ferricyanide and methylene blue. Similarly, guanylate cyclase activation by glyceryl trinitrae plus cysteine, and by NaNO2 plus either a thiol or ascorbate, was inhibited by methemoglobin, ferricyanide and methylene blue. These data suggest that the activation of guanylate cyclase by each of the compounds tested may occur through a common mechanism, perhaps involving nitric oxide. Moreover, these findings suggest that S-nitrosothiols could act as intermediates in the activation of guanylate cyclase by glyceryl trinitrate, NaNO2 and possibly nitroprusside.
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PMID:Requirement of thiols for activation of coronary arterial guanylate cyclase by glyceryl trinitrate and sodium nitrite: possible involvement of S-nitrosothiols. 610 89

Inhibition of human erythrocyte aldehyde dehydrogenase (ALDH) activity was studied using disulfiram and its reduced metabolite, diethyldithiocarbamate (DDC). The enzyme was rapidly inactivated by disulfiram and the inhibition was protected by reduced glutathione (GSH), in a concentration dependent manner when the enzyme premixed with GSH was reacted with disulfiram. Higher reactivity of the thiol group of the enzyme than that of GSH to disulfiram was suggested from the observation that half of the enzyme activity was inhibited when the ratio of disulfiram to GSH was 1:10. Although DDC alone showed no inhibitory effect on the enzyme, inactivation was mediated by a low concentration of heme-containing peroxidases, but not by methemoglobin. Under this condition, the inhibition potential was not protected, even with a high concentration of GSH. The constant reoxidation system of DDC is probably directly related to the enzyme inactivation.
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PMID:Effect of disulfiram and its reduced metabolite, diethyl-dithiocarbamate on aldehyde dehydrogenase of human erythrocytes. 627 37

Human red blood cells treated with the CuZn superoxide dismutase inhibitor diethyldithiocarbamate (DDC) undergo metabolic modifications in addition to the superoxide dismutase inhibition: oxidation of the reduced glutathione (GSH) to oxidized glutathione (GSSG), methemoglobin formation, and increased hexose monophosphate shunt activity were observed. The magnitudes of these changes are dependent on the DDC concentration. Under nitrogen, only superoxide dismutase inhibition occurs. After removal of the GSH with N-ethylmaleimide, production of H2O2 can be detected by measuring the red cell catalase inhibition in the presence of 3-amino-1,2,4-triazole. H2O2 production is not altered by conversion of oxyhemoglobin to methemoglobin by sodium nitrite prior to incubation. GSH oxidation and methemoglobin formation are stopped when DDC is eliminated from the incubation medium after completion of the superoxide dismutase inhibition. These data indicate that methemoglobin formation and modification of the GSH status in red cells treated by DDC are not a direct consequence of the CuZn superoxide dismutase inhibition but are due rather to a DDC-dependent production of H2O2.
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PMID:H2O2 production, modification of the glutathione status and methemoglobin formation in red blood cells exposed to diethyldithiocarbamate in vitro. 627 6

Erythrocytes of Dorset sheep, an animal model with an erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, responded in a dose-dependent manner to the oxidant stress of di- and trichloroacetic acids (DCA and TCA) as measured by increases in methemoglobin (METHB) and decreases in glutathione (GSH). Given the fact that TCA and DCA are now being found in community drinking water supplies at levels greater than 100 micrograms/liter, there is a need to further investigate their effects on biological systems, including those with a compromised ability to deal with oxidant stress (e.g., G-6-PD-deficient erythrocytes).
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PMID:The effects of di- and trichloroacetic acid on sheep erythrocytes: an animal model with a glucose-6-phosphate dehydrogenase deficiency. 649 98

Ascorbic acid significantly reduced the occurrence of sodium nitrite-induced methemoglobin (METHB) formation in a dose-dependent manner in erythrocytes from glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans in vitro. The ascorbic acid treatment, however, also decreased levels of reduced GSH in a dose-dependent manner, a response indicative of oxidant stress to the erythrocyte membrane. The latter findings are inconsistent with the hypothesis that ascorbic acid supplementation in G-6-PD-deficient humans may help compensate for inherently low levels of erythrocyte GSH. Finally, the ascorbic acid-induced reduction of METHB values, while of statistical significance, does not appear to be of clinical significance.
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PMID:The effect of ascorbic acid on sodium nitrite-induced methemoglobin formation in glucose-6-phosphate dehydrogenase-deficient erythrocytes. 661 67

Erythrocytes of both glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans and Dorset sheep, an animal model with an erythrocyte G-6-PD deficiency, responded in a dose-dependent manner to the oxidant stress of methyl oleate ozonide (MOO) as measured by decreases in G-6-PD activity, increases in methemoglobin (METHB) levels, and decreases in GSH. However, the human G-6-PD-deficient erythrocytes were considerably more sensitive to the formation of METHB than the sheep erythrocytes while the reverse was the case for the GSH parameter. The results suggest a qualitative difference in the response of sheep erythrocytes and human G-6-PD-deficient erythrocytes to MOO that seriously questions the value of the sheep erythrocyte as a quantitatively accurate predictive model.
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PMID:An evaluation of the dorset sheep as a predictive animal model for the response of glucose-6-phosphate dehydrogenase-deficient human erythrocytes to a proposed systemic toxic ozone intermediate, methyl oleate ozonide. 661 68


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