Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione S-transferase (GST) isozymes from human fetal liver (16-18 weeks gestation) were purified by affinity chromatography followed by ion-exchange high performance liquid chromatography (HPLC). The purified isozymes were used to investigate toxicity of 1,2-dibromoethane(EDB) in an in vitro model of rat embryos in culture as passive targets. At least five isozymes of GST were found in the human fetal liver. Two anionic forms [pI values 5.5 (P-2) and 4.5 (P-3)] and one basic form [pI value 8.7 (P-6)] were clearly separated. The presence of two near-neutral forms was also identified. All the isozymes of the human fetal liver GSTs tested metabolized EDB (specific activities were 2.1, 7.0, and 2.0 mumol of GSH consumed/min/mg protein for P-2, P-3, and P-6 isozymes, respectively). Covalent binding of EDB to DNA and protein was 144% and 212% higher, respectively, with the P-3 anionic isozyme when compared to the P-6 basic isozyme of GST. No covalent binding to either protein or DNA was observed with the P-2 isozyme. EDB bioactivation by the GST isozyme P-3 (15 units; 1 unit = 1 nmol of GSH consumed/min) resulted in toxicity to cultured rat embryos. Significant reductions of crown rump length, yolk sac diameter, and the composite score of morphological parameters (Brown and Fabro method) were observed. The central nervous system, optic and olfactory systems, and the hind limb were most significantly affected. The results of this investigation suggest that EDB may be classified as a suspected developmental toxicant in humans.
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PMID:A novel model to assess developmental toxicity of dihaloalkanes in humans: bioactivation of 1,2-dibromoethane by the isozymes of human fetal liver glutathione S-transferase. 136 1

Glutathione-dependent defense against xenobiotic toxicity is a multifaceted phenomenon that has been well characterized in mammals. This study undertakes a comparison of two benthic fish species, the channel catfish and brown bullhead, in terms of characteristics of the glutathione system. The channel catfish, a species that has seldom been observed to express pollutant-mediated neoplasia in field studies, was observed to have significantly higher constitutive levels of hepatic total glutathione and reduced glutatione (GSH). Brown bullhead, a species that is often observed to express neoplasia in contaminated systems, had significantly higher hepatic levels of glutathione disulfide. Furthermore, catfish expressed higher levels of activity of the enzymes gamma-glutamylcysteine synthetase (GCS), glutathione reductase (GR), and glutathione S-transferase, whereas bullhead expressed higher hepatic glutathione peroxidase (GPOX) activity. Both species responded to treatment with the redox active quinone, menadione, by expressing elevated hepatic content of total glutathione. However, the induction response was more rapid and more extensive in catfish compared to that in bullhead. This is attributable to the observed interspecific difference in GCS activity. Following treatment with the organic peroxide, tert-butyl hydroperoxide (t-BOOH), bullhead hepatic glutathione was depleted up to 4 hr post-treatment, whereas catfish demonstrated no significant depletion of glutathione in response to t-BOOH. The differing responses to t-BOOH are attributable to interspecific differences in hepatic GPOX and GR activity. Bullhead, therefore, appear to be more susceptible to the effects of GSH arylators and oxidants based upon constitutive levels of glutathione, related enzyme activities, and the response of this system to model xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutathione-dependent defense in channel catfish (Ictalurus punctatus) and brown bullhead (Ameriurus nebulosus). 752 70

Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon-gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN-gamma production. The presence of the reduced form of glutathione (GSH) in the culture medium was found to be essential in these experiments. In the absence of GSH there was an overall 20-fold reduction of the number of IFN-gamma pc in splenocyte cultures of normal or PBS-injected rats, which was further reduced to a 60- to 70-fold-lower level in cultures of rats exposed to HgCl2. This mercury-mediated extra reduction could be fully reversed with an excess (2 mM) of GSH in Lewis but not in BN splenocyte cultures. Since the bivalent Hg2+ ion is known to bind to and inactivate sulfhydryl groups of proteins and low molecular weight thiols, most notably GSH, we investigated a possible role for thiols in IFN-gamma production. It was found that the generation of IFN-gamma pc in normal BN and Lewis splenocyte cultures was strongly dependent on GSH or its precursor cysteine in the culture medium. Other thiol compounds were also effective but disulfides were completely inactive. Depletion of intracellular GSH in ConA-stimulated splenocytes by buthionine sulfoximide (BSO), an inhibitor of de novo GSH biosynthesis, strongly inhibited the generation of IFN-gamma pc. The inhibitory effect of BSO was not abolished by the addition of interleukin-2 (IL-2), but was mimicked with antibodies directed to the IL-2 receptor. The data stress the importance of GSH in the enhancement of IL-2-mediated IFN-gamma production and are most consistent with a model in which mercury interferes with T cell IFN-gamma production by affecting the intracellular availability of GSH. The strain-specific susceptibility to mercury-mediated inhibition of IFN-gamma production is discussed.
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PMID:Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione. 844 15

Ethylene oxide (EO) is a direct-acting mutagen and animal carcinogen used as an industrial intermediate and sterilant with a high potential for human exposure. Understanding the exposure-dose relationship for EO in rodents is critical for developing human EO exposure-dose models. The study reported here examined the dosimetry of EO in male B6C3F1 mice by direct determination of blood EO concentrations. Steady-state blood EO concentrations were measured during a single 4-h nose-only inhalation exposure (0, 50, 100, 200, 300, or 400 ppm EO). In addition, glutathione (GSH) concentrations were measured in liver, lung, kidney, and testis to assess the role of the GSH depletion in the saturable metabolism previously observed in mice (Brown et al., Toxicol. Appl. Pharmacol. 136, 8-19, 1996). Blood EO concentrations were found to increase linearly with exposure concentration up to 200 ppm. Markedly sublinear blood dosimetry was observed at exposure concentrations exceeding 200 ppm. An EO exposure concentration-dependent reduction in tissue GSH levels was observed, with both liver and lung GSH levels significantly depressed at EO exposure concentrations of 100 ppm or greater. Our results also indicate that depletion of GSH is likely responsible for nonlinear dosimetry of EO in mice and that GSH depletion corresponds with reports of dose-rate effects in mice exposed to EO.
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PMID:Ethylene oxide dosimetry in the mouse. 947 28

The aim of this study was to investigate the effects of feed withdrawal and darkening on the antioxidative status of laying hens in high ambient temperatures between 30-40 degrees C. We determined vitamins A and E, lipid peroxidation as thiobarbituric-acid reactive substances (TBARS), glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) in the serum, liver and muscle. Sixteen week old hens (Ross Brown) were divided into 3 groups of 30 hens each. The first group was used as a control. Hens in the second (feed withdrawal) group were subjected to feed removal between 14-18 h during the summer. Hens in the third (darkening) group were subjected to darkening of the hens house with black curtains between 14-18 h. At the end of 16 weeks, blood serum, liver and breast muscle samples were taken from all animals and analysed. Vitamins A and E levels in serum and liver were significantly (P < 0.05, P < 0.01) higher in feed withdrawal and darkened groups than in control group whereas the serum levels of the darkening group were highest. GSH-Px activity and GSH level in liver and muscle were also significantly (P < 0.05, P < 0.01) higher in feed withdrawal and the darkening group than in control. However, TBARS levels in liver and muscle were significantly (P < 0.05, P < 0.01) lower in feed withdrawal and darkening groups compared with control group, whereas the level of the darkening group was the lowest. In conclusion, we observed that feed withdrawal and darkening of hens in high temperatures during summertime resulted in an increase of antioxidant enzymes and vitamins levels and in a decrease of lipid peroxidation.
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PMID:The effects of food withdrawal and darkening on lipid peroxidation of laying hens in high ambient temperatures. 1088 73

Brown cells that are found in the red glands of Mercenaria mercenaria accumulate, detoxify and excrete cadmium. Brown cell involvement in metal detoxification was due in part to endogenous glutathione (GSH) and protein sulfhydryl. Metallothionein (MT) and GSH have been shown to play an important role in metal detoxification in bivalve molluscs. This study showed that the protein sulfhydryl in brown cells of Mercenaria was in fact MT, that brown cell GSH functioned in acute protection against Cd2+ toxicity, that GSH provided the initial defense against Cd2+ toxicity prior to MT induction and that MT variants were unequal in response to Cd2+. During treatment of Mercenaria with 0.5 and 1.0 ppm Cd2+, brown cells were analyzed for MT by capillary electrophoresis and GSH colorimetrically after 0.25, 1, 2, 3, and 4 days. The data indicated that the cadmium-binding protein was MT with an apparent molecular weight of 9 kDa determined by gel filtration or 6 kDa as indicated by capillary electrophoresis. Glutathione appeared to prevail in the brown cell acute response to 0.5 ppm Cd2+, whereas MT appeared to prevail in the acute response to 1.0 ppm Cd2+. Capillary electrophoresis can be used to monitor and quantify MT and its variants in brown cells without need for prior separation of cytosolic components by chromatography. The change in MT-II was greater relative to the change in MT-I in the brown cell acute response to 0.5 ppm Cd2+, whereas the change in MT-1 was greater relative to the change in MT-II in the acute response to 1.0 ppm Cd2+. The variants of brown cell MT appeared to respond differentially to Cd2+ depending upon the Cd2+ treatment concentration.
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PMID:In vivo metallothionein and glutathione status in an acute response to cadmium in Mercenaria mercenaria brown cells. 1124 96

Brown bullheads (Ameriurus nebulosus) are a demersal freshwater species that can be found in a number of polluted ecosystems. The purpose of the present study was to determine the overall capacity for in vitro glutathione S-transferase (GST) detoxification by brown bullheads, and to see if bullhead GST catalysis was altered in bullheads from a polluted site. Brown bullhead liver cytosolic GSTs catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) over a large range of substrate concentrations, with apparent Km and Vmax for CDNB at fixed nucleophile (glutathione, GSH) concentrations of 1.8-1.9 mM and 12.1-14.6 mumol CDNB conjugated/min/mg, respectively. Bullhead GSTs were also highly active toward other substrates such as ethacrynic acid (ECA), delta 5-androstene-3,17-dione (ADI), and nitrobutyl chloride (NBC). Initial rate GST catalytic activities toward CDNB, NBC, ECA, and ADI were significantly lower in female bullheads from a contaminated lake (Lake Apopka Marsh) as compared to female bullheads inhabiting a nearby control site (Lake Woodruff). No site differences were observed with respect to male bullhead GST activities. These studies suggest that brown bullheads efficiently carry out GST conjugation of diverse electrophilic substrates. However, bullhead GST catalysis may be compromised in bullheads inhabiting polluted ecosystems.
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PMID:Altered glutathione S-transferase catalytic activities in female brown bullheads from a contaminated central Florida lake. 1146 Jul 26

The nymphae and different wing-form adults of Brown Planthopper (BPH) were treated intermittently at 34 degrees C, 36 degrees C and 38 degrees C. During the process of heat shock treatment, the variation of the activities of the endogenous enzymes of protective system and the content of lipid peroxides (LPO) in BPH were researched. The results showed that the effect of heat shock treatments on CAT activity in 4th instar of nymphae was higher than that in 3rd and 5th instar. The CAT activity in BPH adults increased with the day-age, and 36 degrees C was the suitable temperature at which H2O2 was scavenged by CAT. The GSH-px activity was higher in old than that in young nymphae, and the ability of GSH-px to scavenge H2O2 was higher in old adults than in those adults emerged early. The activity of SOD had a positive correlation with the treated temperatures, and decreased with the increase of nymphae instar and the day-age of adults after emergence at the same temperature. The activities of CAT, GSH-px, and SOD in macropterous adults were higher than those in brachypterous adults. There were no significant difference for the activities of CAT, GSH-px and SOD between female and male adults (alpha > 0.05). The content of LPO in BPH increased with the rise of treated temperature, and also increased with the increase of instars in nymphae and day-age after emergence in adults at the same temperature. The LPO content was higher in brachypterous than in macropterous adults.
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PMID:[Stress response of Nilaparvata lugens at high temperature and activities of its protective enzyme systems]. 1175 25

The purpose of this study was to characterize the effects of diesel exhaust particles (DEP) on thiol regulation in alveolar macrophages (AM) and lymphocytes. We obtained AM and lymph node (thymic and tracheal) cells (LNC) (at different time points) from rats exposed intratracheally to DEP (5 mg/kg) or saline, and measured inflammatory markers, thiol levels, and glutathione reductase (GSH-R) activity. DEP exposure produced significant increases in neutrophils, lactate dehydrogenase, total protein, and albumin content in the lavage fluid. AM from DEP-exposed rats showed a time-dependent increase in intracellular cysteine (CYSH) and GSH. In LNC the intracellular GSH reached peak level by 24 hr, declining toward control levels by 72 hr after exposure. LNC-CYSH and AM-CYSH and GSH were increased at both 24 and 72 hr. Both Sprague-Dawley and Brown Norway rats showed similar trends of responses to DEP exposure as per measurement of the inflammatory markers and thiol changes. AM and, to a lesser degree, LNC were both active in cystine uptake. The DEP exposure stimulated GSH-R activity and increased the conversion of cystine to CYSH in both cell types. The intracellular level of GSH in DEP-exposed AM was moderately increased compared with the saline control, and was further augmented when cells were incubated with cystine. In contrast, the intracellular level of GSH in DEP-exposed LNC was significantly reduced despite the increased CYSH level and GSH-R activity when these cells were cultured for 16 hr. DEP absorbed 23-31% of CYSH, cystine, and GSH, and only 8% of glutathione disulfide when incubated in cell free media. These results indicate that DEP exposure caused lung inflammation and affected thiol levels in both AM and LNC.
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PMID:Alteration of intracellular cysteine and glutathione levels in alveolar macrophages and lymphocytes by diesel exhaust particle exposure. 1194 Apr 52

Brown Norway rats were exposed by intratracheal instillation of saline, carbon black (CB), or diesel exhaust particles (DEP) (5 mg/kg) on day 1, followed by exposure to ovalbumin (OVA, 90 mg/m(3)) or saline for 30 minutes on days 1, 8, 15, and 29. Animals were sacrificed on day 30. The DEP, CB, or OVA exposure alone did not result in abnormal levels of inflammatory cells, lactate dehydrogenase (LDH), or total protein in the lavage fluid. In combined OVA-DEP or OVA-CB exposure, however, these markers were significantly increased. The adjuvant effect of CB and DEP on OVA sensitization was evidenced by the marked increases in serum OVA-specific IgG (5.6-fold) and IgE (3.5-4 fold) levels, and the increase in interleukin-4 (IL-4) mRNA levels in lung tissue. The OVA exposure markedly reduced glutathione (GSH) levels in both cell types. In combined DEP-OVA exposure, the level of GSH in lymphocytes was further decreased, indicating a possible interactive effect between DEP and OVA exposures. These results show that both DEP and CB augmented OVA-induced allergic sensitization, and that particle composition of DEP may not be a critical factor for the adjuvant effect. OVA exposure causes significant depletion of intracellular GSH in lymphocytes, which may play a key role in OVA-mediated immune responses.
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PMID:The effect of diesel exhaust particles (DEP) and carbon black (CB) on thiol changes in pulmonary ovalbumin allergic sensitized Brown Norway rats. 1209 28


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