Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A previous study revealed that DQ-2511, a new gastroprokinetic drug, induced hemolytic anemia together with increased Heinz body formation, preceded by a marked decrease in erythrocyte reduced glutathione (GSH) content, after 2 weeks of dosing onward in dogs. In this study, the effect of DQ-2511 on erythrocytes in the early period of dosing, in comparison with that of beta-acetylphenylhydrazine (APHZ), was investigated to confirm the difference between this drug and APHZ in the mechanism of increased Heinz body formation. DQ-2511 and APHZ were administered orally to beagle dogs for 1 week at dose levels of 600 and 4 mg/ kg, respectively. Dogs receiving APHZ showed anemia after dosing for 7 days, together with an increase in methemoglobin and Heinz body formation after 3 days of dosing. In contrast, blood GSH, glutathione reductase, and gamma-glutamylcysteine synthetase were only slightly decreased after dosing for 7 days. In dogs treated with DQ-2511, erythrocyte GSH began to decrease after 1 day of treatment and was about 25% of the control value after 7 days; however, no changes were seen in blood glutathione reductase, GSH peroxidase, or gamma-glutamylcysteine synthetase level. Hepatic GSH was decreased slightly. In another experiment, SD rats were administered DQ-2511 and APHZ orally for 1 week at dose levels of 1600 and 15 mg/kg, respectively. Rats receiving DQ-2511 showed no anemia or any changes in erythrocyte GSH and Heinz body formation. In contrast, rats treated with APHZ showed a marked anemia and increases in Heinz body formation and erythrocyte GSH. These results demonstrate that DQ-2511 causes a marked decrease in GSH in dogs, resulting in Heinz body anemia, whereas APHZ induces Heinz body formation after a significant increase in methemoglobin, and suggest that impairment of the GSH redox cycle and synthetases of GSH are not involved in the decreased GSH after DQ-2511 treatment. This difference in effects on GSH content may indicate the existence of a species difference in the anemia induced by DQ-2511.
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PMID:A possible mechanism of heinz body hemolytic anemia induced by DQ-2511, a new gastroprokinetic drug, in dogs. 892 30

The aim of this study was to investigate the effects of 50 Hz magnetic fields (0.2-0.5 mT) on rabbit red blood cells (RBCs) that were exposed simultaneously to the action of an oxygen radical-generating system, Fe(II)/ascorbate. Previous data obtained in our laboratory showed at the exposure of rabbit erythrocytes or reticulocytes to Fe(II)/ascorbate hexokinase inactivation, whereas the other glycolytic enzymes do not show any decay. We also observed depletion of reduced glutathione (GSH) content with a concomitant intracellular and extracellular increase in oxidized glutathione (GSSG) and a decrease in energy charge. In this work we investigated whether 50 Hz magnetic fields could influence the intracellular impairments that occur when erythrocytes or reticulocytes are exposed to this oxidant system, namely, inactivation of hexokinase activity, GSH depletion, a change in energy charge, and hemoglobin oxidation. The results obtained indicate the a 0.5 mT magnetic field had no effect on intact RBCs, whereas it increased the damage with Fe(II)/ascorbate to a 0.5 mT magnetic field induced a significant further decay in hexokinase activity (about 20%) as well as a twofold increase in methemoglobin production compared with RBCs that were exposed to the oxidant system alone. Although further studies will be needed to determine the physiological implications of these data, the results reported in this study demonstrate that the effects of the magnetic fields investigated are able to potentiate the cellular damage induced in vitro by oxidizing agents.
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PMID:In vitro effects of 50 Hz magnetic fields on oxidatively damaged rabbit red blood cells. 908 63

Blast overpressure (BOP) is a phenomenon that describes the instantaneous rise in atmospheric pressure above ambient, resulting from the firing of large caliber weapons or from military or civilian explosions. Exposure to BOP results in injury to the gas-filled organs, such as the lungs, which exhibit a contusion-type injury. We examined the effects of BOP in rats at 5 and 60 min after exposure to a low-level BOP (62 +/- 3 kPa). The exposure was found to cause oxidative stress in the lung that was characterized by 1) a 3.5-fold decrease in total antioxidant reserves, 2) a depletion of the major water-soluble antioxidants ascorbate and glutathione (GSH) by 50 and 75%, respectively, 3) a depletion of lipid-soluble antioxidant vitamin E by 30%, 4) a 2.5-fold increase of fluorescent end products of lipid peroxidation, and 5) an increased methemoglobin (metHb) content at 60 min after exposure. To elucidate the role of released hemoglobin (Hb) in blast-induced oxidative stress, we studied the interactions of oxyhemoglobin (oxyHb), metHb, and the oxoferryl from of Hb free radical species with two physiologically important reductants, ascorbate and GSH. We found that both ascorbate and GSH were able to convert oxyHb to metHb in a reaction that yielded the one-electron oxidation intermediates semidehydroascorbyl radical and glutathionyl radical, respectively. This reaction did not occur under anaerobic conditions, suggesting that oxyHb-bound O2 acted as the electron acceptor. OxyHb induced peroxidation of cis-parinaric acid in the presence but not absence of ascorbate or GSH. Thus the prooxidant action of water-soluble antioxidants via redox cycling of oxyHb and metHb may promote oxidative stress rather than prevent it.
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PMID:Air blast-induced pulmonary oxidative stress: interplay among hemoglobin, antioxidants, and lipid peroxidation. 912 84

Long distance triathlons, due to the large amounts of oxygen uptake they cause, may lead to the generation of reactive oxygen species, and consequently to oxidative stress and damage. We sought to verify this hypothesis. Twelve of the 18 male triathletes who participated in the study took part in a long distance triathlon, the others did not. The prerace blood samples were drawn 48 h before the race and repeatedly until the fourth day of recovery. The myoglobin concentrations increased immediately after the race. The concentrations of methemoglobin, disulfide glutathione (GSSG), and thiobarbituric reactive substances did not significantly change after the race. Although the race induced an inflammatory response, evidenced by the variations in neopterin concentrations and leukocyte counts, there was no consecutive oxidative stress. The basal GSH values were correlated significantly with cycling training volume (r = 0.55) and VO2max (r = 0.53). Muscle damage can occur without evidence of oxidative stress or oxidative damage. We conclude that the magnitude of the antioxidant defense system enhancement depends on training loads. Because of their training status, the triathletes did not suffer from oxidative damage after they finished the long distance triathlon race.
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PMID:No evidence of oxidative stress after a triathlon race in highly trained competitors. 918 72

Oxidative stress causes modification of cellular macromolecules and leads to cell damage. The objective of this study was to identify protein modifications that relate to thiol groups in human red blood cells under oxidative stress. With t-butyl hydroperoxide (t-BH) treatment, results of isoelectric focusing (IEF) analysis showed that two dithiothreitol-reversible modifications are observed, one toward the cathode and the other to the anode. Protein change toward the cathode was demonstrated to be hemoglobin oxidation, which gains a net positive charge, based on the same focus on IEF gels as hemoglobin and methemoglobin and molecular weight analysis by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Otherwise, the change toward the anode was the result of mixed disulfide formation between GSH and protein thiols. Based on the results of molecular weight analysis and its reversion from methemoglobin, protein formed mixed disulfides with GSH were also regarded as hemoglobin. As red blood samples were treated with diamide or GSSG, in addition to the mixed disulfides observed in t-BH-treated cells, additional hemoglobin-GSH mixed disulfide appeared. But the disappearance of this diamide-induced additional mixed disulfide by treating cells with t-BH after diamide treatment suggests that the increase of negative charges from GSH are offset by ferrohemoglobin oxidation to ferrihemoglobin. Additionally, other dithiothreitol-reversible modifications of one cell membrane protein, spectrin, were also observed from the formation of high molecular weight molecules as detected by SDS-PAGE. Results indicate that protein thiols in human red blood cells are susceptible to modification under oxidative stress. IEF analysis provides a useful tool to measure methemoglobin and hemoglobin GSH mixed disulfide formation.
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PMID:Protein thiol modifications of human red blood cells treated with t-butyl hydroperoxide. 930 84

K-Cl cotransport (COT) is the coupled movement of K and Cl, present in most cells, associated with regulatory volume decrease, susceptible to oxidation and functionally overexpressed in sickle cell anemia. The aim of this study was to characterize the effect of the oxidant nitrite (NO2-) on K-Cl COT. NO2- is a stable metabolic end product of the short-lived highly reactive free radical nitric oxide (NO), an oxidant and modulator of ion channels, and a vasodilator. In some systems, the response to NO2- is identical to that of NO. We hypothesized that NO2- activates K-Cl COT. Low potassium (LK) sheep red blood cells (SRBCs) were used as a model. The effect of various concentrations (10(-6) to 10(-1) m) of NaNO2 was studied on K efflux in hypotonic Cl and NO3 media, Cl-dependent K efflux (K-Cl COT), glutathione (GSH), and methemoglobin (MetHb) formation. In support of our hypothesis, K efflux and K-Cl COT were stimulated by increasing concentrations of NaNO2. Stimulation of K efflux was dependent upon external Cl and exhibited a lag phase, consistent with activation of K-Cl COT through a regulatory mechanism. Exposure of LK SRBCs to NaNO2 decreased GSH, an effect characteristic of a thiol-oxidizing agent, and induced MetHb formation. K-Cl COT activity was positively correlated with Methb formation. N-ethyl-maleimide (NEM), a potent activator of K-Cl COT, was used to assess the mechanism of NO2- action. The results suggest that NEM and NO2- utilize at least one common pathway for K-Cl COT activation. Since NaNO2 is also a well known vasodilator, the present findings suggest a role of K-Cl COT in vasodilation.
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PMID:Role of nitrite, a nitric oxide derivative, in K-Cl cotransport activation of low-potassium sheep red blood cells. 984 89

In previous studies performed in this laboratory it was realized that in a broad concentration range (0.5-8 mM) dichromate does not induced red blood cell (RBC) peroxidation. To investigate the reasons behind RBC protection against chromate-induced peroxidation, the effects of 8 mM dichromate on white ghost and RBC peroxidation, RBC antioxidant system and hemoglobin status, as well as RBC osmotic fragility and morphology, were studied in more detail. It was observed that the peroxidation level induced by dichromate on RBCs is practically negligible when compared with the peroxidation induced in white ghosts. Furthermore, the osmotic fragility of RBCs exposed to dichromate is not altered, but the cells undergo echinocytic transformation, probably due to chromate-induced structural RBC membrane modifications. The activities of catalase, gluthatione peroxidase, and superoxide dismutase of RBCs exposed to dichromate were similar to those observed in controls, but the gluthatione reductase and GSH levels were significantly reduced (P<0. 05). Concomitantly, GSSG and methemoglobin levels increased and NADH-methemoglobin reductase activity decreased. These results indicate that chromate does not induce RBC peroxidation, but does promote echinocytic shape transformation, oxidation of hemoglobin and GSH, and inhibition of gluthatione reductase and methemoglobin reductase. The enzymatic antioxidant defense system and hemoglobin oxidation are probably involved in the mechanism of RBC proctection against chromate-induced peroxidation, as is discussed.
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PMID:Human erythrocytes are protected against chromate-induced peroxidation. 1033 Mar 19

The aim of our investigation was to study the red blood cell (RBC) membrane effects of NaNO(2)-induced oxidative stress. Hyperpolarization of erythrocyte membranes and an increase in membrane rigidity have been shown as a result of RBC oxidation by sodium nitrite. These membrane changes preceded reduced glutathione depletion and were observed simultaneously with methemoglobin (metHb) formation. Changes of the glutathione pool (total and reduced glutathione, and mixed protein-glutathione disulfides) during nitrite-induced erythrocyte oxidation have been demonstrated. The rates of intracellular oxyhemoglobin and GSH oxidation highly increased as pH decreased in the range of 7.5-6.5. The activation energy of intracellular metHb formation obtained from the temperature dependence of the rate of HbO(2) oxidation in RBC was equal to 16.7+/-1.6 kJ/mol in comparison with 12.8+/-1.5 kJ/mol calculated for metHb formation in hemolysates. It was found that anion exchange protein (band 3 protein) of the erythrocyte membrane does not participate significantly in the transport of nitrite ions into the erythrocytes as band 3 inhibitors (DIDS, SITS) did not decrease the intracellular HbO(2) oxidation by extracellular nitrite.
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PMID:Membrane effects of nitrite-induced oxidation of human red blood cells. 1051

The effect of enalapril and captopril on total glutathione content (GSSG + GSH) and selenium-dependent glutathione peroxidase (Se-GPx) and glutathione reductase (GSSG-Rd) activities was investigated in mouse tissues. CF-1 mice (4-mo-old females) received water containing enalapril (20 mg/l) or captopril (50 mg/l) for 11 wk. Enalapril increased GSSG + GSH content (P < 0.05) in erythrocytes (147%), brain (112%), and lung (67%), and captopril increased GSSG + GSH content in erythrocytes (190%) and brain (132%). Enalapril enhanced Se-GPx activity in kidney cortex (42%) and kidney medulla (23%) and captopril in kidney cortex (30%). GSSG-Rd activity was enhanced by enalapril in erythrocytes (21%), brain (21%), liver (18%), and kidney cortex (53%) and by captopril in erythrocytes (25%), brain (19%), and liver (34%). In vitro erythrocyte oxidant stress was evaluated by thiobarbituric acid-reactive substances (TBARS) production (control 365 +/- 11, enalapril 221 +/- 26, captopril 206 +/- 17 nmol TBARS x g Hb(-1) x h(-1); both P < 0.05 vs. control) and phenylhydrazine-induced methemoglobin (MetHb) formation (control 66.5 +/- 3.5, enalapril 52.9 +/- 0.4, captopril: 56.4 +/- 2.9 micromol MetHb/g Hb; both P < 0.05 vs. control). Both angiotensin-converting enzyme inhibitor treatments were associated with increased nitric oxide production, as assessed by plasma NO-(3) + NO-(2) level determination (control 9.22 +/- 0.64, enalapril 13.7 +/- 1.9, captopril 17.3 +/- 3.0 micromol NO-(3) + NO-(2)/l plasma; both P < 0.05 vs. control). These findings support our previous reports on the enalapril- and captopril-induced enhancement of endogenous antioxidant defenses and include new data on glutathione-dependent defenses, thus furthering current knowledge on the association of ACE inhibition and antioxidants.
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PMID:Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. 1071 74

Production of nitric oxide (NO) by mitochondrial membranes as methemoglobin formation sensitive to N(G)-methyl-l-arginine inhibition and mitochondrial O(2) consumption in metabolic states 3 and 4 and the respiratory control (state 3/state 4) were measured at early stages of rat thymocyte apoptosis. Programmed cell death was induced by addition of methylprednisolone and etoposide to thymocyte suspensions. Increased NO production by mitochondrial membranes was observed after 30 min of methylprednisolone and etoposide addition and was accompanied by mitochondrial respiratory impairment as an early phenomenon in apoptotic thymocytes. The respiratory control in isolated mitochondria from untreated thymocytes was 4.2 +/- 0.2 and decreased to 3.1 +/- 0.2 and 1.9 +/- 0.3 after 1 h of methylprednisolone and etoposide treatment, respectively. The low mitochondrial respiratory control was accompanied by a marked decrease in GSH and cytochrome c content. Moreover, an inhibitory effect in the amount of apoptosis due to thymocyte pretreatment with N(G)-methyl-l-arginine and N(omega)-nitro-(l)-arginine (l-NNA), indicate that nitric oxide production is closely involved in the signaling of rat thymocyte apoptosis.
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PMID:Nitric oxide production and mitochondrial dysfunction during rat thymocyte apoptosis. 1077 8


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