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

Several recent studies have shown that certain forms of genetic or acquired hypertension are associated with oxidative stress and that animals with those types of hypertension respond favorably to antioxidant therapy. We hypothesize that oxidative stress may cause hypertension via (among other mechanisms) enhanced oxidation and inactivation of nitric oxide (NO). To test this hypothesis, Sprague-Dawley rats were subjected to oxidative stress by glutathione (GSH) depletion by means of the GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L in drinking water) for 2 weeks. The control group was given drug-free drinking water. In parallel experiments, subgroups of animals were provided vitamin E-fortified chow and vitamin C-supplemented drinking water. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of the NO metabolite nitrate plus nitrite, which suggests depressed NO availability. These characteristics were associated with a significant accumulation in various tissues of nitrotyrosine, which is the footprint of NO inactivation by reactive oxygen species. Administration of vitamin E plus vitamin C ameliorated hypertension, improved urinary nitrate-plus-nitrite excretion, and mitigated nitrotyrosine accumulation (despite GSH depletion) in the BSO-treated animals but had no effect in the control group. In conclusion, GSH depletion resulted in perturbation of the NO system and severe hypertension in normal animals. The effects of BSO were mitigated by concomitant antioxidant therapy despite GSH depletion, which supports the notion that oxidative stress was involved in the pathogenesis of hypertension in this model.
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PMID:Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. 1090 27

Reaction of peroxynitrite with the biological ubiquitous CO(2) produces about 35% yields of two relatively strong one-electron oxidants, CO(3) and ( small middle dot)NO(2), but the remaining of peroxynitrite is isomerized to the innocuous nitrate. Partial oxidant deactivation may confound interpretation of the effects of HCO3-/CO(2) on the oxidation of targets that react with peroxynitrite by both one- and two-electron mechanisms. Thiols are example of such targets, and previous studies have reported that HCO3-/CO(2) partially inhibits GSH oxidation by peroxynitrite at pH 7.4. To differentiate the effects of HCO3-/CO(2) on two- and one-electron thiol oxidation, we monitored GSH, cysteine, and albumin oxidation by peroxynitrite at pH 5.4 and 7.4 by thiol disappearance, oxygen consumption, fast flow EPR, and EPR spin trapping. Our results demonstrate that HCO3-/CO(2) diverts thiol oxidation by peroxynitrite from two- to one-electron mechanisms particularly at neutral pH. At acid pH values, thiol oxidation to free radicals predominates even in the absence of HCO3-/CO(2). In addition to the previously characterized thiyl radicals (RS.), we also characterized radicals derived from them such as the corresponding sulfinyl (RSO.) and disulfide anion radical (RSSR.-) of both GSH and cysteine. Thiyl, RSO. and RSSR.- are reactive radicals that may contribute to the biodamaging and bioregulatory actions of peroxynitrite.
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PMID:Carbon dioxide stimulates the production of thiyl, sulfinyl, and disulfide radical anion from thiol oxidation by peroxynitrite. 1113 18

Hepatic blood flow decreases under cholestasis and there is evidence that NO regulates liver microvascular perfusion. Thus, the aim of the present study was to evaluate NO synthesis in cholestasis. Cholestasis was induced by bile-duct ligation (BDL) in male Wistar rats. Bilirubins and enzyme activities were measured in serum. Lipid peroxidation, GSH, GSSG and glycogen were determined in liver. Histopathological analysis was performed. Serum NO2- + NO3- concentration was measured by the Gries reaction. iNOS immunoblot analysis was carried out using an iNOS polyclonal antibody. After 7 days of BDL lipid peroxidation increased while GSH/GSSG ratio decreased. Serum NO2- + NO3- and liver iNOS protein were reduced, accompanied by ischemia as revealed by the histopathological analysis. GSH upregulates NO synthesis by increasing iNOS mRNA levels and iNOS activity, thus the reduction of GSH/GSSG ratio may be responsible for the downregulation of iNOS protein and NO synthesis, which in turn may explain the observed ischemia and the decreased hepatic blood perfusion in cholestasis reported by others.
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PMID:Nitric oxide and inducible nitric oxide synthase expression are downregulated in acute cholestasis in the rat accompanied by liver ischemia. 1124 95

The present study was designed to evaluate the possible protective effect of quercetin, coenzyme Q10 (CoQ10), or L-canavanine treatments against endotoxin-induced shock in rat brain. Shock was induced by i.p. injection of 10 mg x kg(-1)of lipopolysaccharide (LPS) and was biochemically manifested 2 h after injection as an increase in brain malondialdehyde (MDA), total nitrite/nitrate (NO(x)), glutathione peroxidase (GSHPx), and blood lactate level/activity. On the other hand, endotoxemia resulted in reduced brain glutathione (GSH) and phospholipids' content as well as the serum sulfhydryl groups' (SH-group) value. Pretreatment with quercetin (200 mg x kg(-1)per os) 2 h before LPS injection diminished the shock-induced increases in brain MDA, and NO(x)levels while elevating the reduced brain phospholipids' and serum SH groups' content. CoQ10 administered at a dose of 200 mg x kg(-1)per os for 7 days prior to shock induction, reduced the elevated levels of brain MDA, NO(x), and GSHPx level/activity due to redundancy. The same treatment caused a 3-fold increase in the reduced brain GSH level and normalized the depressed phospholipids' content. Treatment of animals with L-canavanine (50 mg x kg(-1)i.p.) simultaneously with LPS injection, reduced the elevated level of blood lactate. Brain superoxide dismutase (SOD) level was neither affected by endotoxin nor by different treatments. In conclusion, this study indicates that SOD may not reflect the level of peroxidation and points to the value of quercetin, CoQ10, and L-canavanine in ameliorating the oxidative status of brain during the early phase of endotoxic shock.
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PMID:Quercetin, coenzyme Q10, and L-canavanine as protective agents against lipid peroxidation and nitric oxide generation in endotoxin-induced shock in rat brain. 1140 18

The ubiquitin/proteasome pathway plays an essential role in protein turnover in vivo, and contributes to removal of oxidatively damaged proteins. We examined the effects of proteasome inhibition on viability, oxidative damage and antioxidant defences in NT-2 and SK-N-MC cell lines. The selective proteasome inhibitor, lactacystin (1 microM) caused little loss of viability, but led to significant increases in levels of oxidative protein damage (measured as protein carbonyls), ubiquitinated proteins, lipid peroxidation and 3-nitrotyrosine, a biomarker of the attack of reactive nitrogen species (such as peroxynitrite, ONOO(-)) upon proteins. Higher levels (25 microM) of lactacystin did not further increase the levels of carbonyls, lipid peroxidation, 3-nitrotyrosine, or ubiquitinated proteins, but produced increases in the levels of 8-hydroxyguanine (a biomarker of oxidative DNA damage) and falls in levels of GSH. Lactacystin (25 microM) caused loss of viability, apparently by apoptosis, and also increased production of nitric oxide (NO.) (measured as levels of NO2- plus NO3-) by the cells; this was inhibited by N-nitro-L-arginine methyl ester (L-NAME), which also decreased cell death induced by 25 microM lactacystin and decreased levels of 3-nitrotyrosine. The NO. production appeared to involve nNOS; iNOS or eNOS were not detectable in either cell type. Another proteasome inhibitor, epoxomicin, had similar effects.
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PMID:Effect of proteasome inhibition on cellular oxidative damage, antioxidant defences and nitric oxide production. 1143 71

Hydrazine is an aircraft fuel and propellant used by the US Air Force. Due to its toxicity the Propulsion Directorate of the Air Force Research Laboratory (AFRL/PR) has investigated alternative chemicals to replace hydrazine. AFRL/PR has synthesized a series of high energy chemicals (HECs), primarily hydrazine derivatives and amino containing compounds such as hydrazinium nitrate (HZN), 2-hydroxyethyl-hydrazine nitrate (HEHN), diethyl hydrazine nitrate (DEHN), ethanolamine nitrate (EAN), histamine dinitrate (HDN) and methoxylamine nitrate (MAN) to study as alternative chemical candidates. Although HECs are reliable constituents of powered propellant systems, they constitute an important class of toxic agents to which military and civilian personnel can be exposed. The current study was undertaken to examine the toxicity of HECs in primary hepatocytes in vitro. The effects of short-term exposure (4 h) of hepatocytes to HECs were investigated with reference to viability, mitochondrial function and oxidative stress markers. The results showed a decrease in mitochondrial activity, increase in lactate dehydrogenase (LDH) leakage and depletion of reduced glutathione (GSH) levels. The levels of reactive oxygen species (ROS) increased dose dependently in HZN, MAN and HDN exposed cells. However, there was no induction of ROS generation in EAN, DEHN and HEHN exposed cells. Depletion of GSH in hepatocytes by buthionine sulfoximine (BSO) prior to exposure to HZN increased its toxicity. The results suggest that at least one mechanism of HEC toxicity is mediated through oxidative stress.
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PMID:In vitro toxicity assessment of a new series of high energy compounds. 1145 92

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.
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PMID:Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. 1150 65

Treatment with Ni(NO3)2 leads to the formation of reactive oxygen species (ROS) in the green alga Scenedesmus acutus f. alternans, causing lipid peroxidation. This effect was stronger in a Ni-sensitive strain, UTEX72, than in a Ni-resistant strain, B4. In the resistant strain, Ni induced an increased ratio of reduced to oxidized glutathione (GSH:GSSG), whereas it caused a lowered ratio in the sensitive strain. Enzymes involved in the control of ROS were studied in these strains as well as two others that have shown different degrees of nickel resistance. The resistant strain, B4, which grows while containing large amounts of internal Ni, had much higher levels of glutathione reductase and catalase than the other strains. The sensitive strain, UTEX72, had higher levels of glutathione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase than did strain B4. The resistant strains, Ni-Tol and Cu-Tol, derived from strain UTEX72, which are partly able to exclude Ni, had enzyme profiles that resembled that of UTEX72 more closely than that of B4. Treatment with 10 and 100 microM Ni for 4 or 22 h had complex effects on enzyme levels in all four strains. Ni decreased glutathione reductase in B4, slightly increased it in Ni-Tol and Cu-Tol, and did not affect the low levels of this enzyme in UTEX72. Ni lowered glutathione peroxidase in B4 and either did not affect it or slightly raised it in the other strains. Ni lowered catalase in B4 and did not affect the other strains. Superoxide dismutase was raised in B4 and Ni-Tol and lowered in Cu-Tol and UTEX72, and glucose-6-phosphate dehydrogenase was lowered in all four strains. These results suggest that one major mechanism of Ni resistance, especially in strain B4, may be the ability to combat the formation of ROS when exposed to this metal, likely by maintaining a high GSH:GSSG ratio.
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PMID:Role of oxidative stress and thiol antioxidant enzymes in nickel toxicity and resistance in strains of the green alga Scenedesmus acutus f. alternans. 1176 59

The incubation of peroxynitrite (PN)-pretreated histone III-S (NH) with Escherichia coli nitrate reductase (cytochrome, NADPH/GSH-independent) and that of NADPH-treated NH (NHNADPH) with liver cytochrome P-450 reductase (NADPH-dependent) resulted in decreased 3-nitrotyrosine immunoreactivity found in Western blot analysis. Additionally, increased nitrate was noted as an end product of these reactions. These findings imply that varied enzymatic denitration/modification of NO/PN-reacted protein, either with or without a reductant, may be important in regulating related signal transduction cascade(s) and relieving oxidative stress.
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PMID:Protein denitration/modification by Escherichia coli nitrate reductase and mammalian cytochrome P-450 reductase. 1181 90

Rats were injected with a single dose of cerous nitrate Ce (NO3)3 (150 mg/kg) intra-peritoneally and killed at 3, 6, 12, 24 and 48 hours later. The results showed that the concentrations of protein and malondialdehyde (MDA) in liver increased, but the concentration of glutathione (GSH) and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione sulfatransferase (GSH-ST) decreased after Ce3+ administration. The results suggest that lipid peroxidation in liver may be an early consequence of Ce3+ exposure and the decrease of GSH might be considered as the cause of lipid peroxidation.
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PMID:[Study on the hepatic toxicity of cerous nitrate in rats]. 1193 13


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