UMLS:C1260386 - FACTA Search

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

Reactive oxygen species (ROS) enhance myocardial ischemia-reperfusion (I/R) injury. Ebselen, a seleno-organic glutathione peroxidase (GPx) mimetic, has a protective effect against tissue injury induced by ROS. However, the cardio-protective effect of orally administered ebselen has never been investigated in cardiac I/R injury. We investigated the effects and mechanisms of orally administered ebselen on experimental myocardial infarction. Isolated perfused rabbit hearts underwent 30 min of global ischemia and 60 min of reperfusion, with or without oral administration of ebselen 24 h before I/R, with or without enhanced oxidative stress by H202 infusion for the first 1 min of reperfusion. The recovery of left ventricular developed pressure (LVDP) was significantly improved, and the myocardial infarct size was significantly reduced by ebselen. The recovery of LVDP and the myocardial infarct size were markedly aggravated by H202 infusion. These enhancements by H202 were dose-dependently suppressed by ebselen, along with a reduction in myocardial 8-hydroxydeoxyguanosine levels, a marker for oxidative DNA damage. The myocardial reduced glutathione (GSH) level was preserved by ebselen. Ebselen markedly enhanced myocardial heat shock protein (HSP) 72 expression. The cardioprotective effect of ebselen-induced HSP72 was confirmed by MTT assay in isolated cardiomyocytes using KNK437, a novel HSP inhibitor. In conclusion, an oral administration of ebselen 24 h before I/R provided excellent cardioprotective effects, at least in part through HSP72 induction and GSH preservation.
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PMID:Oral pretreatment with ebselen enhances heat shock protein 72 expression and reduces myocardial infarct size. 1734 91

The recent finding that acrylamide (AA), a carcinogen in animal experiments and a probable human carcinogen, is formed in foods during cooking raises human health concerns. The relevance of dietary exposure for humans is still under debate. The purpose of the study was to evaluate the possible genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells, a cell line of great relevance to detect genotoxic/antigenotoxic substances, using single cell gel electrophoresis (SCGE) assay and micronucleus test (MNT). In order to clarify the underlying mechanism(s) we evaluated the intracellular generation of reactive oxygen species (ROS) and the level of oxidative DNA damage by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG). The involvement of glutathione (GSH) in the AA-induced oxidative stress was examined through treatment with buthionine sulfoximine (BSO) to deplete GSH. The results indicate that AA caused DNA strand breaks and increase in frequency of MN in HepG2 cells in a dose-dependent manner. The possible mechanism underlies the increased levels of ROS, depletion of GSH and increase of 8-OHdG formation in HepG2 cells treated with AA. We conclude that AA exerts genotoxic effects in HepG2 cells, probably through oxidative DNA damage induced by intracellular ROS and depletion of GSH.
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PMID:Genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells. 1769

The aim of this study was to evaluate the effect of purple sweet potato leaves (PSPLs) consumption on antioxidative status and its modulation of that status in basketball players during training period. Fifteen elite basketball players were enrolled in this study. The seven-week study consisted of a run-in (week 1), PSPLs diet (daily consumption of 200 g PSPLs) (weeks 2, 3), washout (weeks 4, 5), and control diet (low polyphenol, with the amount of carotenoids adjusted to the same level as that of PSPLs) (weeks 6, 7). Blood and urine samples were taken for biochemical analysis. Compared with the control group, the results showed that PSPLs consumption led to a significant increase of plasma polyphenol concentration and vitamin E and C levels. Low density lipoprotein (LDL) lag time was significantly longer in the PSPLs group. A significant decrease of urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was noted; however, there was no significant change in plasma glutathione (GSH), total antioxidant status (TAS) and malondialdehyde + 4-hydroxy-2(E)-nonenal level after consuming the PSPLs diet. In conclusion, consumption of PSPLs diet for 2 weeks may reduce lipid and DNA oxidation that can modulate the antioxidative status of basketball players during training period.
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PMID:Effect of purple sweet potato leaf consumption on the modulation of the antioxidative status in basketball players during training. 1770 27

The present study elucidates a possible mechanism by which chronic organophosphate exposure (dichlorvos 6 mg/kg bw, s.c. for 12 weeks) causes neuronal degeneration. Mitochondria, as a primary site of cellular energy generation and oxygen consumption represent itself a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic dichlorvos exposure on mitochondrial calcium uptake, oxidative stress generation and its implication in the induction of neuronal apoptosis in rodent model. Mitochondrial preparation from dichlorvos (DDVP) treated rat brain demonstrated significant increase in mitochondrial Ca(2+) uptake (644.2 nmol/mg protein). Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase (complex IV) along with altered mitochondrial complex I, and complex II activity, which might have resulted from elevated mitochondrial calcium uptake. The alterations in the mitochondrial calcium uptake and mitochondrial electron transfer enzyme activities in turn might have caused an increase in malondialdehyde, protein carbonyl and 8-hydroxydeoxyguanosine formation as a result of enhanced lipid peroxidation, and as well as protein and mtDNA oxidation. All this could have been because of enhanced oxidative stress, decreased GSH levels and also decreased Mn-SOD activity in the mitochondria isolated from dichlorvos treated rat brain. Thus, chronic organophosphate exposure has the potential to disrupt cellular antioxidant defense system which in turn triggers the release of cytochrome c from mitochondria to cytosol as well as caspase-3 activation in dichlorvos treated rat brain as revealed by immunoblotting experiments. Low-level long-term organophosphate exposure finally resulted in oligonucleosomal DNA fragmentation, a hallmark of apoptosis. These studies provide an evidence of impaired mitochondrial bioenergetics and apoptotic neuronal degeneration after chronic low-level exposure to dichlorvos.
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PMID:Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. 1785 Aug 75

1. Oxygen free radicals are important components involved in the pathophysiological processes observed during ischaemia-reperfusion (I/R). The present study was designed to assess the possible protective effect of alpha-lipoic acid (ALA) on renal I/R injury. 2. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min renal pedicle occlusion followed by 24 h reperfusion. Saline or ALA (100 mg/kg, i.p.) was administered 15 min prior to ischaemia and immediately before the reperfusion period. At the end of 24 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity were measured in serum samples, whereas tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, 8-hydroxydeoxyguanosine (8-OHdG) and total anti-oxidant capacity (AOC) were assayed in plasma samples. 3. Kidney samples were taken for the determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels, as well as Na(+)/K(+)-ATPase and myeloperoxidase (MPO) activity. The formation of reactive oxygen species in renal tissue samples was monitored using a chemiluminescence (CL) technique with luminol and lucigenin probes. Oxidant-induced tissue fibrosis was determined by tissue collagen content and the extent of tissue injury was analysed microscopically. 4. Ischaemia-reperfusion caused a significant increases in blood creatinine, BUN, LDH, IL-1beta, IL-6, TNF-alpha and 8-OHdG, whereas AOC was decreased. In kidney samples from the I/R group, MDA, MPO, collagen and CL levels were found to be increased significantly; however, glutathione levels and Na(+)/K(+)-ATPase activity were decreased. Conversely, ALA treatment reversed all these biochemical indices, as well as histopathological alterations induced by I/R. 5. In conclusion, these data suggest that ALA reverses I/R-induced oxidant responses and improves microscopic damage and renal function. Thus, it seems likely that ALA protects kidney tissues by inhibiting neutrophil infiltration, balancing the oxidant-anti-oxidant status and regulating the generation of inflammatory mediators.
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PMID:Alpha-lipoic acid protects against renal ischaemia-reperfusion injury in rats. 1794 95

A comparative evaluation is reported of pro-oxidant states in 82 patients with ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control donors. These disorders display cancer proneness, and/or early aging, and/or other clinical features. The measured analytes were: (a) leukocyte and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c) plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as follows: WS>BS approximately FA approximately XP>DS approximately AT approximately controls. Urinary 8-OHdG levels were significantly increased in a total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was significantly increased in patients with WS and in young (< or =15 years) patients with DS or with FA and decreased in older patients with DS or FA and in AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly increased in patients with WS, FA, and DS. The UA and AA levels were significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP patients. Rationale for chemoprevention trials is discussed.
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PMID:Different patterns of in vivo pro-oxidant states in a set of cancer- or aging-related genetic diseases. 1805 16

Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer.
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PMID:Aberrant expression of selenoproteins in the progression of colorectal cancer. 1805 26

Trichloroethylene (TCE) is an environmental and industrial pollutant whose hepatotoxicity has been demonstrated in experimental animals. However, the mechanisms of the effects, in particular those related to its genotoxicity in humans, are not well understood. The aim of this study was to assess the genotoxic effects of TCE and to identify and clarify the mechanisms, using human hepatoma HepG2 cells. Exposure of the cells to TCE caused significant increase of DNA migration in comet assay and of micronuclei (MN) frequencies at all tested concentrations (0.5-4mM), respectively, which suggests that TCE caused DNA strand breaks and chromosome damage. The involvement of lipid peroxidation in the genotoxic properties of TCE was confirmed by using immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS). To elucidate the role of glutathione (GSH) in these effects, the intracellular GSH level was modulated by pre-treatment with buthionine-(S,R)-sulfoximine (BSO), a specific GSH synthesis inhibitor, and by co-treatment with N-acetylcysteine (NAC), a GSH precursor. It was found that depletion of GSH in HepG2 cells with BSO dramatically increased the susceptibility of HepG2 cells to TCE-induced cytotoxicity and DNA damage, while when the intracellular GSH content was elevated by NAC, the DNA damage induced by TCE was almost completely prevented. These results indicate that TCE exerts genotoxic effects in HepG2 cells, probably through DNA damage by oxidative stress; GSH, as a main intracellular antioxidant, is responsible for cellular defense against TCE-induced DNA damage.
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PMID:Possible involvement of oxidative stress in trichloroethylene-induced genotoxicity in human HepG2 cells. 1828 23

The chemoprotective effect of hydroxytyrosol (HT) against Sudan I-induced genotoxicity was investigated in a human hepatoma cell line, HepG2. The comet assay and micronucleus (MN) assay were used to monitor genotoxicity. Intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe, 2,7-dichlorofluorescein diacetate (DCFH-DA). The levels of oxidative DNA damage and lipid peroxidation were estimated by immunocytochemistry analysis of 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), respectively. Intracellular glutathione (GSH) level was estimated by fluorometric methods. The results showed that HT significantly reduced the genotoxicity caused by Sudan I. Furthermore, HT ameliorated lipid pexidation as demonstrated by a reduction in TBARS formation and attenuated GSH depletion in a concentration-dependent manner. It was also found that HT reduced intracellular ROS formation and 8-OHdG level caused by Sudan I. These results strongly suggest that HT has significant protective ability against Sudan I-induced genotoxicity.
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PMID:Inhibition of Sudan I genotoxicity in human liver-derived HepG2 cells by the antioxidant hydroxytyrosol. 1829 12

Hydroquinone (HQ) is used as an antioxidant in rubber industry and as a developing agent in photography. HQ is also an intermediate in the manufacture of rubber, food antioxidant and monomer inhibitor. However, the mechanisms of the effects, in particular those related to its genotoxicity in humans, are not well understood. The aim of this study was to assess the genotoxic effects of HQ and to identify and clarify the mechanisms, using human hepatoma HepG2 cells. DNA strand breaks and DNA-protein crosslinks (DPC) were measured by the proteinase K-modified alkaline single cell gel electrophoresis (SCGE) assays. Using the SCGE assay, a significant dose-dependent increment in DNA migration was detected at concentrations of HQ (6.25-25 microM); but at the higher tested concentrations (50 microM), a reduction in the migration compared to the maximum migration at 25 microM was observed. Post-incubation with proteinase K significantly increased DNA migration in cells exposed to higher concentrations of HQ (50 microM). A significant increase of the frequency of micronuclei was found in the range from 12.5 to 50 microM in the micronucleus test (MNT). The data suggested that HQ caused DNA strand breaks, DPC and chromosome breaks. To elucidate the oxidative DNA damage mechanism, the 2,7-dichlorofluorescein diacetate (DCFH-DA) and o-phthalaldehyde (OPT) were chosen to monitor the levels of reactive oxygen species (ROS) and glutathione (GSH), respectively. The present study showed that HQ induced the increased levels of ROS and depletion of GSH in HepG2 cells, the doses being 25-50 and 6.25-50 microM, respectively. Moreover, HQ significantly caused 8-hydroxydeoxyguanosine (8-OHdG) formation in HepG2 cells at concentrations from 12.5 to 50 microM. All these results demonstrate that HQ exerts genotoxic effects in HepG2 cells, probably through DNA damage by oxidative stress. GSH, as a main intracellular antioxidant, is responsible for cellular defense against HQ-induced DNA damage.
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PMID:Hydroquinone-induced genotoxicity and oxidative DNA damage in HepG2 cells. 1835 59

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