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

Moderate physical activity when performed on a regular basis presents a number of benefits to the whole organism, especially regarding immune system function, such as augmenting resistance to infections and to cancer growth. Although glutamine production by active muscle cells as well as neuroendocrine alterations mediated by the chronic adaptation to exercise may play a role, the entire mechanism by which exercise makes the immune system aware of challenges remains mostly uncovered. This is particularly true for the effects of an acute exercise session on immune function. In this work, circulating monocytes/macrophages from sedentary rats submitted to an acute (1 h) swimming session were tested for the ability of phagocytosing zymosan particles, phorbol myristate acetate (PMA)-induced hydrogen peroxide production, nitric oxide (NO) release (assessed by nitrate and nitrite production) and the expression of NO synthases (NOS-1, NOS-2 and NOS-3). The results showed that an exercise bout induced a 2.4-fold rise in macrophage phagocytic capacity (p = 0.0041), a 9.6-fold elevation in PMA-induced hydrogen peroxide release into the incubation media (1-h, p = 0.0022) and a 95.5%-augmentation in nitrite basal production (1-h incubation; p = 0.0220), which was associated with a marked expression of NOS-2 (the inducible NOS isoform; p = 0.0319), but not in other NOS gene products. Although NOS-2 expression is nuclear factor-kappaB (NF-kappaB)-dependent, no systemic oxidative stress was found, as inferred from the data of plasma TBARS and glutathione disulphide (GSSG) to glutathione (GSH) ratio in circulating blood erythrocytes which remained constant after the acute exercise. Also, no stressful situation seemed to be faced by monocytes/macrophages, since the expression of the 70-kDa heat shock protein (HSP70) remained unchanged. We conclude that NF-kappaB-dependent induction of NOS-2 and macrophage activation must be related to local factor(s) produced in the surroundings of monocytes/macrophages.
 ...
PMID:Acute exercise stimulates macrophage function: possible role of NF-kappaB pathways. 1690 27

Mechanical ventilation (MV) is associated with diaphragmatic oxidative stress that contributes to both diaphragmatic atrophy and contractile dysfunction. However, the pathways responsible for oxidant production in the diaphragm during MV remain unknown. To address this issue, we tested the hypothesis that diaphragmatic nitric oxide synthase (NOS) activity is elevated during MV, resulting in nitration of diaphragmatic proteins. Rats were mechanically ventilated for 18 h, and time-matched, anesthetized but spontaneously breathing animals served as controls. Protein levels of endothelial NOS, inducible NOS, and neuronal NOS were measured in diaphragms from all animals. 3-Nitrotyrosine levels were also measured as an index of protein nitration, and S-nitrosothiol levels were measured as a marker of nitric oxide reactions with molecules containing sulfhydryl groups. Levels of nitrates and nitrites were measured as markers of stable end products of nitric oxide metabolism. Finally, as a marker of oxidative stress, diaphragmatic levels of reduced GSH were also analyzed. MV did not promote an increase in diaphragmatic protein levels of endothelial NOS or neuronal NOS. Moreover, inducible NOS was not detected in the diaphragms of either experimental group. Consistent with these findings, MV did not elevate diaphragmatic 3-nitrotyrosine levels in any subcellular fraction of the diaphragm, including the cytosolic, mitochondrial, membrane, and insoluble protein fractions. Moreover, prolonged MV did not elevate diaphragmatic levels of S-nitrosothiols, nitrate, or nitrite. Finally, prolonged MV significantly reduced diaphragmatic levels of GSH, which is consistent with diaphragmatic oxidative stress. Collectively, these data reveal that MV-induced oxidative stress in the diaphragm is not due to increases in nitric oxide production by NOS.
 ...
PMID:Diaphragmatic nitric oxide synthase is not induced during mechanical ventilation. 1693 63

Obesity continues to be an increasing health problem in worldwide and antiobesity drugs have commonly been used by obese patients. During the use of anorectic drugs, the antioxidant defense may be affected, especially by reactive oxygen species. It was decided to investigate the effects of dexfenfluramine on body weight, daily food intake, brain thiobarbituric acid-reactive substances (TBARS), glutathione (GSH) and nitric oxide (NO) levels, and 5-HT immunoreactivity. Mice were divided into two groups each containing 8 Swiss Albino adult (6 months) mice. Group 1, untreated, was used as a control; group 2 was treated with dexfenfluramine 0.4 mg/kg per day intraperitoneally for 7 days. Brain TBARS and GSH levels were assayed spectrophotometrically. The stable end-products of NO, nitrite and nitrate, were analyzed spectrophotometrically. Brain tissue 5-HT immunoreactivity was observed using an immunohistochemical method. There were significant decreases in body weight in the dexfenfluramine group (p < 0.05). Although brain GSH and NO(x) levels decreased significantly, brain TBARS levels increased in the dexfenfluramine group (p < 0.05). Brain 5-HT immunoreactivity also increased in the dexfenfluramine-treated group compared to control. In conclusion, our findings show that dexfenfluramine is effective in achieving weight loss and also increases lipid peroxidation in mouse brain.
 ...
PMID:The effects of dexfenfluramine administration on brain serotonin immunoreactivity and lipid peroxidation in mice. 1700 98

Nitroglycerin (GTN) tolerance was induced in vivo (rats) and in vitro (rat and human vessels). Electrochemical detection revealed that the incubation dose of GTN (5x10(-6) mol/L) did not release NO or modify O(2) consumption when administered acutely. However, development of tolerance produced a decrease in both mitochondrial O(2) consumption and the K(m) for O(2) in animal and human vessels and endothelial cells in a noncompetitive action. GTN tolerance has been associated with impairment of GTN biotransformation through inhibition of aldehyde dehydrogenase (ALDH)-2, and with uncoupling of mitochondrial respiration. Feeding rats with mitochondrial-targeted antioxidants (mitoquinone [MQ]) and in vitro coincubation with MQ (10(-6) mol/L) or glutathione (GSH) ester (10(-4) mol/L) prevented tolerance and the effects of GTN on mitochondrial respiration and ALDH-2 activity. Biotransformation of GTN requires functionally active mitochondria and induces reactive oxygen species production and oxidative stress within this organelle, as it is inhibited by mitochondrial-targeted antioxidants and is absent in HUVECrho(0) cells. Experiments analyzing complex I-dependent respiration demonstrate that its inhibition by GTN is prevented by mitochondrial-targeted antioxidants. Furthermore, in presence of succinate (10x10(-3) mol/L), a complex II electron donor added to bypass complex I-dependent respiration, GTN-treated cells exhibited O(2) consumption rates similar to those of controls, thus suggesting that complex I was affected by GTN. We propose that, following prolonged treatment with GTN in addition to ALDH-2, complex I is a target for mitochondrially generated reactive oxygen species. Our data also suggest a role for mitochondrial-targeted antioxidants as therapeutic tools in the control of the tolerance that accompanies chronic nitrate use.
 ...
PMID:Complex I dysfunction and tolerance to nitroglycerin: an approach based on mitochondrial-targeted antioxidants. 1705 93

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.
 ...
PMID:Melatonin protects against epirubicin-induced cardiotoxicity. 1710 37

Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study examined the effect of NF-kappaB inhibitor and antioxidant, pyrrolidinedithiocarbamate (PDTC) on experimental ulcerative colitis in rats. Animals were randomly divided into 4 groups, each consisting of 6 animals; normal control group, acetic acid group, PDTC-treated group and sulfasalazine-treated group as a positive control group. Induction of colitis by intracolonic administration of 3% acetic acid produced severe macroscopic inflammation in the colon 24 h after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, oedema and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), and nitrite/nitrate and colonic concentrations of tumor necrosis factor-alpha (TNF-alpha) and the neutrophil infiltration index, myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxides formation and depleted reduced glutathione concentrations (GSH) in colonic tissues. Immunohistochemical studies of colonic sections revealed upregulation of inducible nitric oxide synthase (iNOS). Pretreatment with PDTC at a dose of (200 mg/kg/day, i.p.), three days before induction of colitis decreased serum LDH, nitrite/nitrate and TNF-alpha levels, colonic concentrations of MPO and lipid peroxides while increased colonic GSH concentration. Moreover, PDTC pretreatment attenuated colonic iNOS expression. Finally, histopathological changes were nearly restored by PDTC pretreatment. The findings of the present study provide evidence that PDTC may be beneficial in patients with inflammatory bowel disease.
 ...
PMID:Ameliorative effect of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats. 1711 1

The fathead minnow is a useful species for evaluating the toxicity of wastewater effluents. While this fish is widely used for "survival" studies of metal toxicity, little or no work has been done on the tissue distribution of metals in fathead minnows. To determine the distribution of tissue lead, aquarium studies were conducted for several weeks with fish maintained in soft synthetic freshwater. Lead- (II) nitrate was added to three aquaria attaining concentrations of 20-30 ppb (aquarium B), 100-140 ppb (aquarium C), and roughly 200 ppb (aquarium D). Results were compared to controls (aquarium A). During the initial week, the majority of aquarium D fish died, whereas few deaths occurred in the other groups. Lead accumulation was dose- and tissue-dependent, with highest uptake by the gills. Gill concentrations of aquarium D fish averaged about 4-fold higherthan in skeleton or skin and muscle. In vitro, lead (2.5-25 ppm) caused dose-dependent reductions in the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) in gills incubated in physiological buffer. These findings demonstrate that fathead minnow gills bind and accumulate waterborne lead rapidly and preferentially and raise the possibility that gill lipid peroxidation contributes to lead toxicity at low water hardness.
 ...
PMID:Tissue lead concentration during chronic exposure of Pimephales promelas (fathead minnow) to lead nitrate in aquarium water. 1714 21

Daunorubicin is an anthracycline antitumour agent that can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure. Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving daunorubicin-induced superoxide anion production have been proposed. In the present study, we showed that ebselen a seleno-organic compound exhibiting glutathione peroxidase-like and antioxidant activities, significantly ameliorated daunorubicin-induced cardiomyopathy. Subcutaneous administration of ebselen to daunorubicin-treated rats showed significant improvement in serum cardiac indices including creatine kinase isoenzyme and lactate dehydrogenase as well as serum glutathione (GSH) peroxidase. Moreover, myocardium of daunorubicin/ebselen-treated rats showed significant improvement in daunorubicin-induced depletion of GSH peroxidase activity and reduced glutathione content, in addition to attenuation of daunorubicin-induced increase in cardiac malondialdehyde production and total nitrate/nitrite concentration levels. These results were confirmed by histopathological examination of ventricles of daunorubicin/ebselen-treated rats that revealed significant improvement of the characteristic cardiomyopathic changes induced by daunorubicin treatment. Interestingly, control rats treated with ebselen showed significant elevation in serum lactate dehydrogenase activity, cardiac malondialdehyde production and total nitrate/nitrite concentration levels compared with the untreated control animals. In conclusion, ebselen treatment significantly alleviates daunorubicin-induced cardiomyopathy.
 ...
PMID:Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats. 1716 21

: Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite-nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite-nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.
 ...
PMID:Effects of levetiracetam in lipid peroxidation level, nitrite-nitrate formation and antioxidant enzymatic activity in mice brain after pilocarpine-induced seizures. 1720 90

Disruption of leptin signaling in the heart may contribute to obesity-related cardiac disease, as leptin deficient (oblob) mice display cardiac hypertrophy, increased cardiac apoptosis and reduced survival. Since leptin maintains a tonic level of neuronal nitric oxide synthase (NOS1) expression in the brain, we hypothesized that leptin deficiency would decrease NOS1 cardiac expression, in turn activating xanthine oxidoreductase (XOR) and creating nitroso-redox imbalance. We studied 2- to 6-month-old oblob (n=26) and C57Bl/6 controls (n=27). Cardiac NOS1 protein abundance (P<0.01) and mRNA expression (P=0.03) were reduced in oblob (n=10 and 6, respectively), while NOS3 protein abundance and mRNA expression were unaltered. Importantly, cardiac NOS1 protein abundance was restored towards normal in oblob mice after leptin treatment (n=3; P<0.05 vs leptin untreated oblob mice). NO metabolite (nitrite and nitrate) production within the myocardium was also reduced in oblob mice (n=5; P=0.02). Furthermore, oxidative stress was increased in oblob mice as GSH/GSSG ratio was decreased (n=4; P=0.02). Whereas XOR activity measured by Amplex Red fluorescence was increased (n=8; P=0.04), XOR and NADPH oxidase subunits protein abundance were not changed in oblob mice (n=6). Leptin deficiency did not disrupt NOS1 subcellular localization, as NOS1 co-localized with ryanodine receptor but not with caveolin-3. In conclusion, leptin deficiency is linked to decreased cardiac expression of NOS1 and NO production, with a concomitant increase in XOR activity and oxidative stress, resulting in nitroso-redox imbalance. These data offer novel insights into potential mechanisms of myocardial dysfunction in obesity.
 ...
PMID:Reduced neuronal nitric oxide synthase expression contributes to cardiac oxidative stress and nitroso-redox imbalance in ob/ob mice. 1730 68


<< Previous 1 2 3 4 5 6 7 8 9 10