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 potential cytotoxic effects of the compounds 8-quinolinol, chloramine-T and natamycin have been studied in isolated pig hepatocytes. The relative cytotoxicity of these compounds was evaluated on the basis of the leakage of cytosolic lactate dehydrogenase (LDH), 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction by mitochondrial dehydrogenases, uptake of neutral red (NR) by cytosolic lysosomes, glutathion (GSH) depletion and oxidized glutathion (GSSG) efflux after 24 h exposure. Evaluation of the 20%, 50% and 80% reduced absorbance data obtained from the parameters NR20, NR50, and NR80, and MTT20, MTT50 and MTT80 enabled us to rank these compounds in decreasing order of cytotoxicity: 8-quinolinol > natamycin > chloramine-T. Also for the parameters LDH and GSH, chloramine-T appears to be less cytotoxic than natamycin and 8-quinolinol. Our study demonstrated that pig hepatocytes may be a useful model for examining cytotoxic events of drugs to be used in pigs, therefore avoiding possible extrapolation problems due to species differences.
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PMID:Cytotoxicity in pig hepatocytes induced by 8-quinolinol, chloramine-T and natamycin. 1074 41

Salvia miltiorrhiza (SM) is a traditional Chinese herbal medicine, commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that SM exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we evaluated the molecular mechanism of SM in a human hepatoma cell line, HepG(2). Our results show that SM exerted clear cytotoxic effects, and strongly inhibited the proliferation of HepG(2) cells. It was also observed that SM treatment caused apoptotic cell death as evaluated by: (a), morphological changes by using acridine orange/ethidium bromide staining; (b), DNA fragmentation by TdT-mediated dUTP nick end labeling (TUNEL); and (c), sub-G(1) cell analysis. Furthermore, depletion of intracellular glutathione (GSH) and reduction of mitochondrial membrane potential were found to be involved in the initiation of apoptosis by SM.
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PMID:Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG(2) cells. 1077 35

Dihydrolipoamide dehydrogenase (LADH) from Trypanosoma cruzi was inactivated by treatment with myeloperoxidase (MPO)-dependent systems. With MPO/H2O2/NaCl, LADH lipoamide reductase and diaphorase activities significantly decreased as a function of incubation time. Iodide, bromide, thiocyanide and chloride effectively supplemented the MPO/H2O2 system, KI and NaCl being the most and the least effective supplements, respectively. LADH inactivation by MPO/H2O2/NaCl and by NaOCl was similarly prevented by thiol compounds such as GSH, L-cysteine, N-acetylcysteine, penicillamine and N-(2-mercaptopropionyl-glycine) in agreement with the role of HOCI in LADH inactivation by MPO/H2O2/NaCl. LADH was also inactivated by MPO/NADH/halide, MPO/H2O2/NaNO2 and MPO/NADH/NaNO2 systems. Catalase prevented the action of the NADH-dependent systems, thus supporting H2O2 production by NADH-supplemented LADH. MPO inhibitors (4-aminobenzoic acid hydrazide, and isoniazid), GSH, L-cysteine, L-methionine and L-tryptophan prevented LADH inactivation by MPO/H2O2/NaNO2. Other MPO systems inactivating LADH were (a) MPO/H2O2/chlorpromazine; (b) MPO/H2O2/monophenolic systems, including L-tyrosine, serotonin and acetaminophen and (c) MPO/H2O2/di- and polyphenolic systems, including norepinephrine, catechol, nordihydroguaiaretic acid, caffeic acid, quercetin and catechin. Comparison of the above effects and those previously reported with pig myocardial LADH indicates that both enzymes were similarly affected by the MPO-dependent systems, allowance being made for T. cruzi LADH diaphorase inactivation and the greater sensitivity of its LADH lipoamide reductase activity towards the MPO/H2O2/NaCl system and NaOCl.
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PMID:Trypanosoma cruzi dihydrolipoamide dehydrogenase is inactivated by myeloperoxidase-generated "reactive species". 1082 17

Reactive oxygen species (ROS) are implicated as agents of cellular damage in pulmonary oxygen toxicity. Glutathione (GSH) and GSH-dependent antioxidant enzymes protect against damage by ROS, and recycling of glutathione disulfide (GSSG) to GSH by glutathione reductase (GR) is essential for the optimum functioning of this system. Exposure to hyperoxia inhibits lung development in newborn animals and humans, and attenuates cell growth in proliferating cell cultures. Considerable evidence supports a role for ROS as growth-altering molecules. Previously, we have observed that gene transfer of GR to mitochondria in H441 cells, using a vector containing a mitochondrial leader sequence (LGR), protected these cells against t-BuOOH-induced cytotoxicity. The present studies tested the hypothesis that gene transfer of LGR would attenuate the cytostatic effects of hyperoxia exposure in H441 cells. H441 cells (0.9 x 10(6) cells/plate) transfected with adenovirus containing LGR or the complementary DNA (cDNA) for manganese superoxide dismutase in reverse orientation (DOS) as a control construct, and untransfected cells (CON) were maintained in 21% oxygen (normoxia) or 95% oxygen (hyperoxia) for 48 h, and cell growth was assessed by cell counts and by reduction of the tetrazolium dye 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to formazan. Cells maintained in normoxia achieved normal growth (CON, 1.98; DOS, 1.91; LGR, 2.0 x 10(6) cells/plate). Hyperoxia inhibited cell growth and the reduction of MTT; however, cells transfected with LGR had greater mitochondrial GR activities (CON, 16+/-2; DOS, 19+/-3; LGR, 322+/-18 mU/mg of protein), sustained more normal growth patterns (CON, 1.25+/-0.12; DOS, 1.24 +/-0.21, LGR, 1.8+/-0.25 x 10(6) cells/plate), and had less inhibition of MTT reduction (CON, 29; DOS, 27; LGR, 16% inhibition, P<0.01) after exposure to hyperoxia for 48 h than was observed in cells transfected with DOS or in control cells not infected with virus. In addition, resistant cells had higher mitochondrial GSH levels and maintained mitochondrial GSH/GSSG ratios in hyperoxia, suggesting that maintaining mitochondrial GSH homeostasis determined critical aspects of cell division in these studies. The mechanisms for sustaining cell growth during hyperoxia in H441 cells with enhanced mitochondrial GR activities are unknown, but similar effects in infants exposed to supplemental oxygen could be highly beneficial.
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PMID:Attenuation of hyperoxia-induced growth inhibition in H441 cells by gene transfer of mitochondrially targeted glutathione reductase. 1083 71

Glutamate toxicity on PC12 cells is mediated by oxidative stress as a consequence of the inhibition of a cystine uptake system with depletion of GSH. In this study we report that glutamate decreases PC12 cell viability, inhibiting the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). This decrease was prevented by the antioxidants vitamin E, idebenone and L-deprenyl, which were also shown to be effective in reducing the accumulation of reactive oxygen species (ROS) in cells exposed to glutamate, decreasing the fluorescence of 2',7'-dichlorofluorescein (DCF). Incubation of PC12 cells with high glutamate concentrations induced mitochondrial dysfunction, leading to the loss of mitochondrial transmembrane potential, evaluated as a decrease in rhodamine 123 (Rh123) retention by mitochondria, and to the decrease of intracellular ATP levels. The mitochondrial dysfunction, induced by glutamate, can be involved in the observed increase of [Ca2+]i. The elevation of [Ca2+]i occurred after GSH depletion, suggesting that oxidative stress is involved in the disturbances of intracellular calcium homeostasis. In conclusion, our data indicate that glutamate, at concentrations which block cystine uptake in PC12 cells leading to GSH depletion and inducing oxidative stress, increases ROS accumulation and decreases cell survival by a mechanism involving mitochondrial dysfunction and impairment of Ca2+ homeostasis.
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PMID:Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation of intracellular Ca2+ homeostasis. 1094 Apr 57

Calf thymus DNA was treated with authentic HOCl, and hypohalous acid-generating systems. This caused a decrease in fluorescence of ethidium-DNA complexes when ethidium bromide was subsequently added to the DNA. The fluorescence continued to decrease up to 30 min after adding HOCl. Loss in fluorescence was proportional to the concentration of HOCl and was complete when a 3-fold excess of HOCl was added to the DNA. No significant decrease in the fluorescence was observed when the chlorination was carried out in the presence of a concentration of monochlorodimedone (MCD) equivalent to that of HOCl. MCD is known to react stoichiometrically with HOCl. The decrease in fluorescence was completely inhibited by H2O2, ascorbate and glutathione (GSH). We have estimated the rate constant for the reaction of HOCl with H2O, to be 1-2 x 10(5) M(-1)s(-1). When compared with authentic HOCl, HOCl-generating systems (Cl + H2O2 + MPO or chloroperoxidase) were found to be inefficient in damaging DNA. This result most likely arises because the rate constant for reaction of HOCl with H2O2 is about 1000-fold faster than that for the reaction with DNA. HOBr and HOI generating systems also had a limited ability to damage DNA. We conclude that good chlorine acceptors and antioxidants protect DNA from hypohalous acid-induced oxidative damage.
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PMID:Dissociation of DNA double strand by hypohalous acids. 1099 80

Adenophora triphylla (AT), an oriental medicinal plant, was extracted using water and several organic solvents and each fraction was assayed for its tumoricidal effects on human Jurkat T cells with 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT). The influence on induction of apoptosis and G1 arrest was also examined. The ethyl acetate fraction showed the most pronounced inhibitory effects on proliferation of Jurkat T cells. Apoptosis was induced in line with up-regulation of FasL, tyrosine phosphorylation and c-fos mRNA levels. Arrest in G1 of the cell cycle was observed in A2780 cells with a wild type p53 gene but not HT-29 cells with a mutant p53 gene. Modifying effects of AT on cell turnover and glutathione(GSH) levels in vivo were also investigated in the stomach of rats given 150 mg/kg of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gavage and then fed a diet supplemented with 5% or 1% pulverized AT and 0.5% or 0.2% ethylacetate-extracted AT for 42 hours. The 5% AT and both of the ethylacetate fractions caused significant reduction in proliferating cell nuclear antigen (PCNA)-labeling in the glandular stomach epithelium as compared with the value for the MNNG alone group. In addition, the treatments significantly increased the gastric GSH levels. These results suggest that AT could be a chemopreventive agent against gastric cancer.
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PMID:Suppressive effects of Adenophora triphylla extracts on in vitro tumor cell growth and in vivo gastric epithelial proliferation. 1106 47

Eosinophil peroxidase has been implicated in promoting oxidative tissue damage in a variety of inflammatory conditions, including asthma. It uses H(2)O(2) to oxidize chloride, bromide and thiocyanate to their respective hypohalous acids. The aim of this study was to establish which oxidants eosinophil peroxidase produces under physiological conditions. By measuring rates of H(2)O(2) utilization by the enzyme at neutral pH, we determined the catalytic rate constants for bromide and thiocyanate as 248 and 223 s(-1) and the Michaelis constants as 0.5 and 0.15 mM respectively. On the basis of these values thiocyanate is preferred 2.8-fold over bromide as a substrate for eosinophil peroxidase. Eosinophil peroxidase catalysed substantive oxidation of chloride only below pH 6.5. We found that when eosinophil peroxidase or myeloperoxidase oxidized thiocyanate, another product besides hypothiocyanite was formed; it also converted methionine into methionine sulphoxide. During the oxidation of thiocyanate, the peroxidases were present as their compound II forms. Compound II did not form when GSH was included to scavenge hypothiocyanite. We propose that the unidentified oxidant was derived from a radical species produced by the one-electron oxidation of hypothiocyanite. We conclude that at plasma concentrations of bromide (20-120 microM) and thiocyanate (20-100 microM), hypobromous acid and oxidation products of thiocyanate are produced by eosinophil peroxidase. Hypochlorous acid is likely to be produced only when substrates preferred over chloride are depleted. Thiocyanate should be considered to augment peroxidase-mediated toxicity because these enzymes can convert relatively benign hypothiocyanite into a stronger oxidant.
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PMID:Substrates and products of eosinophil peroxidase. 1148 72

To determine the enhancing effect of a whey protein isolate on the cytotoxicity of a potential anticancer drug, baicalein, the human hepatoma cell line Hep G2 was assigned to grow in different media for four days, and cell growth and apoptosis were investigated. The control group was grown in normal medium; the other three groups were grown in whey protein isolate (Immunocal) medium, baicalein medium, and a combination of Immunocal and baicalein. As indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, survival rate was significantly lower in cells grown in baicalein + Immunocal than in cells grown in baicalein alone. In contrast, there was no significant difference in survival rate of the cells grown in Immunocal. In the investigation of apoptosis, cells grown in baicalein + Immunocal showed a higher phosphatidylserine exposure, lower mitochondrial transmembrane potential, and nearly 13 times more cells undergoing apoptosis than cells grown in baicalein alone. We also demonstrated that Immunocal reduced glutathione (GSH) in Hep G2 cells by 20-40% and regulated the elevation of GSH, which was in response to baicalein. In conclusion, Immunocal seemed to enhance the cytotoxicity of baicalein by inducing more apoptosis; this increase in apoptotic cells may be associated with the depletion of GSH in Hep G2 cells. This is the first study to demonstrate, in vitro, that Immunocal may function as an adjuvant in cancer treatments.
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PMID:Enchancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug. 1152 98

Hydroxychavicol (HC; 10 - 50 microM), a betel leaf component, was found to suppress the 2% H(2)O(2)-induced lucigenin chemiluminescence for 53 - 75%. HC (0.02 - 2 microM) was also able to trap superoxide radicals generated by a xanthine/xanthine oxidase system with 38 - 94% of inhibition. Hydroxyl radicals-induced PUC18 plasmid DNA breaks was prevented by HC (1.6 - 16 microM). A 24-h exposure of KB cells to HC (0.5, 1 mM) resulted in 54 - 74% cell death as analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. HC (10, 50 microM) further suppressed the growth of KB cells (15 and 76%, respectively). Long-term colony formation of KB cells was inhibited by 51% with 10 microM HC. Pretreatment of KB cells with 100 microM HC inhibited the attachment of KB cells to type I collagen and fibronectin by 59 and 29%, respectively. Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5 mM led to apoptosis as revealed by detection of sub-G(0)/G(1) peaks with a concomitant decrease in the number of cells residing in late S and G(2)/M phase. Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in reduced form of GSH (>0.2 mM) and the increasing of reactive oxygen species production (>0.1 mM) as analysed by CMF- and DCF-single cell fluorescence flow cytometry. These results indicate that HC exerts antioxidant property at low concentration. HC also inhibits the growth, adhesion and cell cycle progression of KB cells, whereas its induction of KB cell apoptosis (HC>0.1 mM) was accompanied by cellular redox changes.
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PMID:Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species. 1183 9


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