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)

The effect of oxidants on K(+)-Cl(-) cotransport (KCC) was investigated in equine red blood cells. Carbon monoxide mimicked O(2). The substituted benzaldehyde, 12C79 (5 mM), markedly increased O(2) affinity. In N(2), however, O(2) saturation was low (<10%) but KCC remained active. Nitrite (NO(2)(-)) oxidized heme to methemoglobin (metHb). High concentrations of NO(2)(-) (1 and 5 mM vs. 0.5 mM) increased KCC activity above control levels; it became O(2) independent but remained sensitive to other stimuli. 1-Chloro-2, 4-dinitrobenzene (1-3 mM) depleted reduced glutathione (GSH). Prolonged exposure (60-120 min, 1 mM) or high concentrations (3 mM) stimulated an O(2)-independent KCC activity; short exposures and low concentrations (30 min, 0.5 or 1 mM) did not. The effect of these manipulations was correlated with changes in GSH and metHb concentrations. An oxy conformation of Hb was necessary for KCC activation. An increase in its activity over the level found in oxygenated control cells required both accumulation of metHb and depletion of GSH. Findings are relevant to understanding the physiology and pathology of regulation of KCC.
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PMID:Oxidants and regulation of K(+)-Cl(-) cotransport in equine red blood cells. 1100 78

Oxidant stress, in vivo or in vitro, is known to induce oxidative changes in human red blood cells (RBCs). Our objective was to examine the effect of augmenting RBC glutathione (GSH) synthesis on 1) degenerative protein loss and 2) RBC chemokine- and free radical-scavenging functions in the oxidatively stressed human RBCs by using banked RBCs as a model. Packed RBCs were stored up to 84 days at 1-6 degrees C in Adsol or in the experimental additive solution (Adsol fortified with glutamine, glycine, and N-acetyl-L-cysteine). Supplementing the conventional additive with GSH precursor amino acids improved RBC GSH synthesis and maintenance. The rise in RBC gamma-glutamylcysteine ligase activity was directly proportional to the GSH content and inversely proportional to extracellular homocysteine concentration, methemoglobin formation, and losses of the RBC proteins band 3, band 4.1, band 4.2, glyceraldehyde-3-phosphate dehydrogenase, and Duffy antigen (P < 0.01). Reduced loss of Duffy antigen correlated well with a decrease in chemokine RANTES (regulated upon activation, normal T-cell expressed, and secreted) concentration. We conclude that the concomitant loss of GSH and proteins in oxidatively stressed RBCs can compromise RBC scavenging function. Upregulating GSH synthesis can protect RBC scavenging (free radical and chemokine) function. These results have implications not only in a transfusion setting but also in conditions like diabetes and sickle cell anemia, in which RBCs are subjected to chronic/acute oxidant stresses.
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PMID:Glutathione protects chemokine-scavenging and antioxidative defense functions in human RBCs. 1124 4

Bed rest is an integral part of treatment of numerous diseases. Typical examples are bone fractures of lower extremities and pelvis. Temporary immobilization is necessary also, e.g., in heart diseases (stroke), backbone and imminent abortion. The sick organism spares energy during the bed rest wich is beneficial. However, bed rest results in many alterations which are disadavantageous. They concern the function of almost all organs and systems but affect most significantly the locomotor and ciruclatory systems. Bed rest brings also about changes in the composition of peripheral blood and functions of the morphotic elements of blood. Red blood cells are subjected to the action of large amounts of reactive oxygen species (ROS). During oxidation of hemoglobin to methemoglobin superoxide radical anion (O2-) is formed: HbFe2+ + O2 --> MetHbFe3+ + O2- (1) Ferrous and ferric ions present in the cytoplasm of red blood cells may be catalysts of the Fenton reaction leading to the production of the hydroxyl radical: O2- + Fe3+ --> O2- + Fe2+ (2) Fe2+ + H2O2 --> Fe3+ + OH + HO- (3) OH shows a tremendous reactivity. It may react with lipids, proteins, nucleic acids and carbohydrates. The process of lipid peroxidation is best understood. It concerns mainly polyunsaturated fatty acids present in cell membranes. Peroxidation of membrane lipids decreases membrane fluidity and impairs its barrier function. The lowered membrane fluidity compromises erythrocyte deormability which in turn disturbs oxygen delivery to the tissues. End productions of lipid peroxidation are low-molecular wieght compounds, among them carbohydrates (ethane and pentane) and aldehydes, e.g. malondialdehyde (MDA). MDA concentration is an acknowldeged marker of the intensity of lipid peroxidation. Erythrocytes contain a complex system of protection against the action of ROS. It includes various enzymatic and non-enzymatic mechanism. The most important antioxidative enzymes of the red blood cells are superoxide dismutase (Cu,Zn-SOD, EC 1.15.1.1) catalase (CAT, EC 1.11.1.6) and glutathione peroxidase (GSH-Px, EC 1.11.1.9). Cu,Zn-SOD catalyzes the dismuation of O2- to hydrogen peroxide (H2O2). Catalase and peroxidase remove H2O2 and, moreover, GSH-Px can reduce lipid peroxides. Under normal conditions an equilibrium exists between the formation and removal ROS. If ROS are formed in excess or the defensive antioxidative mechanism are inefficient, oxidative stress develops. Derangement of the equilibrium between the formation and removal of ROS is important in the pathosgenesis of many diseases, e.g. atherosclerosis, diabetes, Down syndrome and Alzheimer disease. There are literature data on disturbances of enzymatic antioxidant defense mechanism of blood plateless during bed rest. This study was aimed at an examination of the post-traumatic bed rest on the enzymatic antioxidative defense mechanisms and lipid peroxidation in erythrocytes.
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PMID:Effect of long term bed rest in men on enzymatic antioxidative defence and lipid peroxidation in erythrocytes. 1154 39

The effect of virus inactivation by 1,9-dimethylmethylene blue (DMMB) phototreatment, methylene blue (MB) phototreatment or heat on the activities of antioxidant systems of stroma-free hemoglobin (SFH) was studied. DMMB photoinactivated human immunodeficiency virus by > 3.69 log10 under conditions that inactivated 3.33 log10 of vesicular stomatitis virus (VSV). Under conditions which inactivated VSV by 6.10 log10 (1.37 J/cm2 irradiation and 2 microM DMMB), there was little change in the methemoglobin (Met-Hb) formation, concentration of reduced glutathione (GSH), or superoxide dismutase (SOD), catalase (CAT) or glutathione peroxidase (GPX) activities. However, the activity of glutathione reductase (GR) was decreased by 77%. Under conditions that inactivated VSV by 5.69 log10 (1.37 J/cm2 irradiation and 24 microM MB) there was little effect of MB phototreatment on SOD, CAT, GPX and GSH activities. However, GR activity was decreased by 74% and Met-Hb content reached 3.98%. Under conditions that inactivated VSV by more than 6.20 log10 (60 degrees C for 2 min), virucidal heat treatment resulted in 27% Met-Hb formation and decreased GPX activity by 43%. No significant decline in SOD, CAT or GR activities or GSH concentration was observed. These results suggest that, compared with heat treatment and MB phototreatment, virucidal DMMB treatment preserves not only the oxidative state of hemoglobin but also the antioxidant systems against superoxide and hydrogen peroxide, although the reduced GR activity may limit the quenching capacity of antioxidants in DMMB-treated SFH.
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PMID:Comparison of the effects of different antiviral treatments on the antioxidant systems of stroma-free hemoglobin. 1159 61

Menadione is selectively toxic to erythrocytes. Although GSH is considered a primary target of menadione, intraerythrocyte thiolic alterations consequent to menadione exposure are only partially known. In this study alterations of GSH and protein thiols (PSH) and their relationship with methemoglobin formation were investigated in human and rat red blood cells (RBC) exposed to menadione. In both erythrocyte types, menadione caused a marked increase in methemoglobin associated with GSH depletion and increased oxygen consumption. However, in human RBC, GSH formed a conjugate with menadione, whereas, in rat RBC it was converted to GSSG, concomitantly with a loss of protein thiols (corresponding to menadione arylation), and an increase in glutathione-protein mixed disulfides (GS-SP). Such differences were related to the presence of highly reactive cysteines, which characterize rat hemoglobin (cys beta125). In spite of the greater thiol oxidation in rat than in human RBC, methemoglobin formation and the rate of oxygen consumption elicited by menadione in both species were rather similar. Moreover, in repeated experiments under N2 or CO-blocked heme, it was found that menadione conjugation (arylation) in both species was not dependent on the presence of oxygen or the status of heme. Therefore, we assumed that GSH (human RBC) and protein (rat RBC) arylation was equally responsible for increased oxygen consumption and Hb oxidation. Moreover, thiol oxidation of rat RBC was strictly related to methemoglobin formation.
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PMID:The pro-oxidant role of protein SH groups of hemoglobin in rat erythrocytes exposed to menadione. 1180 31

We have examined the structure-activity relationships in methemoglobin (MetHb) formation by high explosives 2,4,6-trinitrotoluene (TNT), 2,4,6-trinitrophenyl-N-nitramine (tetryl) and 2,4,6-trinitrophenyl-N-nitraminoethylnitrate (pentryl), and a number of model nitrobenzenes. In lysed human erythrocytes the rate constants of oxyhemoglobin (OxyHb) oxidation increased with an increase in single-electron reduction potential (E(1)7) or with a decrease of the enthalpies of single-electron reduction of nitroaromatics. Tetryl and pentryl oxidized OxyHb almost 3 times faster than TNT. Although the initial rates of MetHb formation in intact erythrocytes by tetryl, pentryl, and TNT matched their order of reactivity in the oxidation of OxyHb in lysed erythrocytes, TNT was a more efficient MetHb forming agent than tetryl and pentryl during a 24-h incubation. The decreased efficiency of tetryl and pentryl was attributed to their reaction with intraerythrocyte reduced glutathione (GSH) producing 2,4,6-trinitrophenyl-Sglutathione, which acted as a less efficient OxyHb oxidizing agent.
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PMID:Methemoglobin formation in human erythrocytes by nitroaromatic explosives. 1183 72

Treatment of cyanide poisoning generally includes methemoglobin forming agents, like amyl nitrite and/or sodium nitrite (SN), in combination with sodium thiosulphate (STS). However, in many instances of cyanide poisoning, use of nitrites are contraindicated due to their strong vasoactive properties. alpha-Ketoglutarate (alpha-KG) antagonises cyanide by cyanohydrin formation and is considered a promising antidote for cyanide poisoning. In the present study, pre-treatment (30 min) and simultaneous treatment (0 min) of alpha-KG (5 mM) was found to confer significant protection against 5 mM potassium cyanide (KCN) induced cytotoxicity in rat thymocytes as measured by eosin Y exclusion and leakage of intracellular lactate dehydrogenase (LDH), but could not prevent the mitochondrial dysfunction (MTT assay), depletion of cellular GSH (reduced glutathione) and DNA damage. The post-treatment (5 or 30 min) of alpha-KG did not offer any protection on any of the above parameters. Results of in vitro studies were also supported by in vivo data. Pre-treatment of peroral (p.o.) alpha-KG (0.125-2.0 g/kg) exhibited dose and time dependent effects and was found to be effective even when given upto 60 min prior to KCN (p.o.). Addition of STS significantly enhanced the protective efficacy of alpha-KG at all the doses and time intervals. A 10 min pre-treatment of alpha-KG increased the LD(50) of KCN 7.6-fold, which was further increased to 25.6-fold by the addition of both SN and STS. Simultaneous treatment of alpha-KG (2.0 g/kg) increased the LD50 of KCN 5.4-fold which was increased to 18.1-fold by the addition of STS. However, addition of SN did not confer any additional protection. In the presence of SN+STS, a decrease in the dose of alpha-KG exhibited a dose-dependent decrease in protection, but still a >10-fold protection could be observed at 1.0 g/kg dose of alpha-KG. Considering the efficacy and safety of peroral alpha-KG, a promising treatment regimen consisting of alpha-KG+STS or alpha-KG+SN+STS is proposed, depending upon the individual situation.
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PMID:In vitro and in vivo attenuation of experimental cyanide poisoning by alpha-ketoglutarate. 1186 29

S-adenosylmethionine (SAMe) is reported to have hepatoprotective and antioxidant functions. Acetaminophen (paracetamol) was used to induce oxidative damage in cats, and to then determine the effect of SAMe treatment on erythrocyte morphology, PCV, liver histopathology, thiobarbituate reacting substances (TBARS), reduced glutathione (GSH), and oxidised glutathione (GSSG). Cats receiving acetaminophen had a significant increase in methemoglobin and Heinz body production. A significant effect for the interaction of time and treatment was found for Heinz body production and changes in PCV. No significant changes were found in blood or hepatic TBARS. Blood GSH increased significantly in all cats, while the blood GSH:GSSG ratio tended to increase the most in cats given acetaminophen only. The hepatic GSH:GSSG ratio tended to increase in cats given SAMe and decrease in cats given acetaminophen, but this effect was not significant. SAMe protected erythrocytes from oxidative damage by limiting Heinz body formation and erythrocyte destruction and maybe useful in treating acetaminophen toxicity.
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PMID:S-adenosylmethionine (SAMe) in a feline acetaminophen model of oxidative injury. 1267 Apr 31

This study was conducted to explore the relationship between physicochemical property and toxic effectiveness using rat red blood cells (RBCs). The toxic effectiveness of acid nonsteroidal anti-inflammatory drugs (NSAIDs) was systemically examined by the depletion of intracorpuscular adenosine triphosphate (ATP), glutathione (GSH), and hemoglobin (Hb) at various doses, increased every 5 fmol/RBC. When the RBCs were incubated with NSAIDs, the drugs attained maximum levels within RBC, and the levels were then reduced. The ATP depletion seemed to be observed on the excretion of the drugs prior to the depletions of GSH and Hb. The physicochemical properties of NSAIDs were obtained from QMPRPlus, SMILES code, and CS ChemRaw Ultra. Correlation between their physicochemical properties and their doses for the depletions of ATP, GSH and Hb was performed in comparison with those of the membrane bound enzyme (MBE) inhibiting- and methemoglobin (MHb)-generating drugs. The ATP depletion by NSAIDs was correlated with the GSH depletion and intracorpuscular levels of the drugs, but not with the Hb depletion. The GSH depletion was correlated with the Hb depletion and participated in the lipophilicity of the drugs.
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PMID:Correlation between the physicochemical property of some nonsteroidal anti-inflammatory drugs and changes in adenosine triphosphate, glutathione and hemoglobin in rat erythrocytes. 1291 68

Primaquine is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium spp. Methemoglobinemia and hemolytic anemia, however, are dose-limiting side effects of primaquine therapy. These hemotoxic effects are believed to be mediated by metabolites, although the identity of the toxic specie(s) and the mechanism underlying hemotoxicity have remained unclear. Previous studies showed that an N-hydroxylated metabolite of primaquine, 6-methoxy-8-hydroxylaminoquinoline, was capable of mediating primaquine-induced hemotoxicity. The present studies were undertaken to investigate the hemolytic potential of 5-hydroxyprimaquine (5-HPQ), a phenolic metabolite that has been detected in experimental animals. 5-HPQ was synthesized, isolated by flash chromatography, and characterized by NMR spectroscopy and mass spectrometry. In vitro exposure of (51)Cr-labeled erythrocytes to 5-HPQ induced a concentration-dependent decrease in erythrocyte survival (TC(50) of ca. 40 microM) when the exposed cells were returned to the circulation of isologous rats. 5-HPQ also induced methemoglobin formation and depletion of glutathione (GSH) when incubated with suspensions of rat erythrocytes. Furthermore, when red cell GSH was depleted (>95%) by titration with diethyl maleate to mimic GSH instability in human glucose-6-phosphate dehydrogenase deficiency, a 5-fold enhancement of hemolytic activity was observed. These data indicate that 5-HPQ also has the requisite properties to contribute to the hemotoxicity of primaquine. The relative contribution of N-hydroxy versus phenolic metabolites to the overall hemotoxicity of primaquine remains to be assessed.
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PMID:Primaquine-induced hemolytic anemia: susceptibility of normal versus glutathione-depleted rat erythrocytes to 5-hydroxyprimaquine. 1472 25


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