Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male B6C3F1 mice were exposed to 4000 ppm methylene chloride (MC) for 6 hr/day, 5 days/week for up to 13 weeks. Groups of mice were killed at intervals from Day 2 to Week 13. Whole lungs were examined morphologically, immunocytochemically, and biochemically. Biochemical and morphological examination was also performed on isolated Clara cells. The major initial morphological effect seen in lungs was acute Clara cell damage after one exposure to MC. However, this damage appeared to resolve after five consecutive daily exposures to MC. After a 2-day interval the Clara cell lesion reappeared on subsequent reexposure to MC. However, the severity of the lesion decreased over the duration of the study. The appearance and disappearance of the lesion in the Clara cell correlated well with the activity of cytochrome P450 monooxygenase in the Clara cell as assessed immunocytochemically (cytochromes P450IIB 1 and 2) in the whole lung and biochemically in the freshly isolated Clara cell (determined by ethoxycoumarin O-dealkylation and aldrin epoxidation). When there was a marked decrease in cytochrome P450 monooxygenase activity the lesion was not present. This suggested that with time the lung (Clara cell) has developed tolerance to MC possibly due to the inactivation of a cytochrome P450 isozyme. The glutathione S-transferase metabolism of MC by the lung cytosol remained virtually unaltered throughout the study. Events accompanying the discussed changes include (1) a significant increase in nonprotein sulfhydryl in the lungs of all exposed animals, (2) altered plating characteristics of the isolated Clara cells from exposed lungs after 24 hr in culture, and (3) an increase in the number of bronchiolar cells in the S-phase after the first exposure to MC. The study also demonstrates the advantages of target cell isolation and study over whole lung biochemical investigation alone.
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PMID:Methylene chloride--an inhalation study to investigate pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days. 137 20

The tumor promotion potential of 2,3',4,4',5-pentachlorobiphenyl (PCB-118) was studied in a two-stage initiation/promotion bioassay in female Sprague-Dawley rats. The animals were initiated by intraperitoneal administration of N-nitrosodiethylamine after partial hepatectomy. After 5 weeks of recovery, the promotion period commenced by once-weekly subcutaneous administrations of PCB-118 at six dose levels (10, 40, 160, 640, 2500, and 10,000 microg/kg body weight/week) for 20 weeks. In addition, three of these dose levels (40, 640, and 10,000 microg/kg body weight/week) were administered for 52 weeks. Evaluation of hepatic foci positive for glutathione S-transferase P demonstrated that the mono-ortho chlorine substituted congener PCB-118 significantly increased the number of foci/cm3 of liver in the two highest dose groups after 20 weeks, but did not significantly increase the percentage of the liver occupied by foci. After 52 weeks of treatment, both the percentage and the number of foci/cm3 were significantly increased in the highest dose group. A toxic equivalency factor based on foci development during 20 weeks of treatment would be less than 0.00002. Altered relative liver and thymus weights were observed after treatment with both substances as well as an induction of methyl cholanthrene- and phenobarbital-inducible isoenzymes of cytochrome P450 monooxygenase. These results show that PCB-118 has a potency to enhance foci growth in rat liver, although the potency is low compared to that of structurally related compounds.
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PMID:Promotion of altered hepatic foci by 2,3',4,4',5-pentachlorobiphenyl in Sprague-Dawley female rats. 902 79

The filamentous fungus Cunninghamella elegans has the ability to metabolize xenobiotics, including polycyclic aromatic hydrocarbons and pharmaceutical drugs, by both phase I and II biotransformations. Cytosolic and microsomal fractions were assayed for activities of cytochrome P450 monooxygenase, aryl sulfotransferase, glutathione S-transferase, UDP-glucurono-syltransferase, UDP-glucosyltransferase, and N-acetyltransferase. The cytosolic preparations contained activities of an aryl sulfotransferase (15.0 nmol min-1 mg-1), UDP-glucosyltransferase (0.27 nmol min-1 mg-1) and glutathione S-transferase (20.8 nmol min-1 mg-1). In contrast, the microsomal preparations contained cytochrome P450 monooxygenase activities for aromatic hydroxylation (0.15 nmol min-1 mg-1) and N-demethylation (0.17 nmol min-1 mg-1) of cyclobenzaprine. UDP-glucuronosyltransferase activity was detected in both the cytosol (0.09 nmol min-1 mg-1) and the microsomes (0.13 nmol min-1 mg-1). N-Acetyltransferase was not detected. The results from these experiments provide enzymatic mechanism data to support earlier studies and further indicate that C. elegans has a broad physiological versatility in the metabolism of xenobiotics.
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PMID:Phase I and phase II enzymes produced by Cunninghamella elegans for the metabolism of xenobiotics. 902 50

The larvicidal effects of polyphenols from dietary alder leaf litter were investigated in different field collections of three detritivorous Aedes taxa (Ae. detritus, Ae. cataphylla, Ae. rusticus) and compared to the cytochrome P450 monooxygenase, glutathione S-transferase, and esterase activities. Larvae from polyphenol-rich habitats had a higher tolerance for polyphenols and higher midgut cytochrome P450 and esterase activities than larvae from polyphenol-poor habitats. Furthermore, the role of P450 enzymes in the mechanism of resistance to alder polyphenols was suggested by the synergistic effect in vivo of piperonyl butoxide in the resistant Ae. rusticus. This confirms the importance of polyphenols to larval mosquito performance, and provides evidence for the importance of specific detoxification mechanisms for tolerance to dietary polyphenols. Arch.
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PMID:Comparative ability to detoxify alder leaf litter in field larval mosquito collections. 1091 9

We investigated the mechanisms conferring resistance to methyl-parathion (44-fold) and to methomyl (8-fold) in Tetranychus urticae from Greece by studying the effect of synergists on the resistance and the kinetic characteristics of various enzymes in a resistant strain (RLAB) and a susceptible reference strain (SAMB). It is shown that S,S,S-tributyl phosphorotrithioate, a synergist that inhibits esterases and glutathione S-transferases, and piperonyl butoxide, a synergist that inhibits cytochrome P450 mediated monooxygenases, did not affect the level of methyl-parathion or methomyl resistance in RLAB and that resistance ratios to both insecticides did not change significantly in the presence of either synergist. Isoelectric focusing of esterase allozymes on single mites revealed no differences in staining intensity and glutathione S-transferase activity was not significantly different in the two strains. The activity of two cytochrome P450 monooxygenase groups was compared. No significant difference of 7-ethoxyresorufin-O-diethylase activity was observed between strains that were two-fold higher in RLAB than in SAMB. The kinetic characteristics of acetylcholinesterase, the target enzyme of organophosphates and carbamates, revealed that acetylcholinesterase in RLAB was less sensitive to inhibition by paraoxon and methomyl in comparison with SAMB. I(50), the inhibitor concentration inducing 50% decrease of acetylcholinesterase activity was greater (119- and 50-fold with paraoxon and methomyl, respectively) and the bimolecular constant k(i) was lower (39- and 47-fold with paraoxon and methomyl, respectively) in RLAB compared to SAMB.
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PMID:Mechanisms of resistance to organophosphates in Tetranychus urticae (Acari: Tetranychidae) from Greece. 1188 76

A comparative study has been performed on populations of Unionidae from the Lake Suszek and Brda river situated in the centre of Tucholski Landscape Park, around which there are no factories and the Pilica river--affected by the influence of the nearby town agglomeration. Mussels collected from Suszek were also treated (72 h) with various concentrations of dichlorophenol (DCP; 0.1, 0.15, 0.2 ppm) and paraquat (PQ; 1, 5, 10 ppm) in laboratory conditions (aquarium). The activities of glutathione S-transferase (GST) and cytochrome P450 monooxygenase system (NAD(P)H ferricyanide reductase, NAD(P)H cytochrome c reductase), cytochrome P450 content and b(5) in microsomal and cytosolic fractions of digestive gland were investigated. The differences in enzyme activities between groups of mussels, which were exposed to various concentrations of chemical pollutants, as well as the dependence on geographical distribution in Poland, were observed. In experiments with DCP the dose-dependent increase in GST activity was found, but no changes after PQ treatment were observed. Results, in experiments with DCP and PQ, have varied from no change to increase or decrease in the measured monooxygenase activities and cytochrome P450 content. Increases have been recorded in two cases (NADPH ferricyanide reductase and cytochrome P450) after exposure to DCP and in the case of NADH ferricyanide reductase following the exposure to PQ. NAD(P)H cytochrome c reductase activity and content of P450 decreased considerably in 5 and 10 ppm PQ-treated mussels. Thus, the treatment with DCP and PQ in water changed the properties of the mussels digestive gland cytochrome P450 monooxygenase system. These changes may be used as a bioindicator, at the molecular level, of exposure to those xenobiotics not only in controlled experiments (aquaria) but also in the natural environment.
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PMID:Comparative study of the xenobiotic metabolising system in the digestive gland of the bivalve molluscs in different aquatic ecosystems and in aquaria experiments. 1229 71

The effect of the administration of Thonningia sanguinea (T. S.) on the abundance of individual components of the cytochrome P450 monooxygenase enzyme was examined using Western blotting and competitive reverse-transcriptase-polymerase chain reaction (RT-PCR). We also investigated the time-course of inhibition of T. S. on drug metabolizing enzymes. A single intraperitoneal dose of T. S. extract (5 ml/kg) suppressed CYP, cytochrome b5 and NADPH-CYP reductase activity by 45%, 34% and 22% respectively 24 h after T. S. administration. While T. S. did not have any significant effect on microsomal glutathione S-transferase activity, it inhibited p-nitrophenol hydroxylase (PNPH, CYP2E1) and 7-methoxyresorufin O-demethylase (MROD, CYP 1A2) activities by 37% and 32% respectively at 12 h post-T. S. administration. PNPH, erythromycin N-demethylase (ERDM, CYP 3A1/2) and MROD activities were inhibited by 28-36% 24 h after T. S. injection. Consistent with these observations, the levels of CYP2E1, CYP1A2 and CYP3A2 proteins were also suppressed 24 h post-T. S. administration. While CYP2E1 mRNA was unaffected by T. S. administration, CYP1A2 and CYP3A2 mRNAs were decreased by T. S. Cytosolic glutathione S-transferase activity was increased by 30%, 6 h after T. S injection. These data demonstrate that administration of T. S. differentially affect CYP isoforms in the liver of rats and that T. S. selectively suppresses CYP3A2 and CYP1A2 gene expression.
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PMID:Selective suppression of cytochrome P450 gene expression by the medicinal herb, Thonningia sanguinea in rat liver. 1474 31

The toxicity of fipronil to insecticide-susceptible houseflies and the cross-resistance potential of fipronil were determined for six insecticide-resistant laboratory housefly strains by topical application and feeding bioassay. The insecticide-resistant strains represented different levels and patterns of resistance to pyrethroids, organophosphates, carbamates and organochlorines. Five strains were almost susceptible to fipronil in feeding bioassay with resistance factors at LC50 between 0.36 and 3.0. Four of these strains were almost susceptible to topically applied fipronil (resistance factors at LD50 were 0.55, 0.83, 3.3 and 2.5, respectively), whereas one strain was 13-fold resistant to topically applied fipronil. A highly gamma-HCH-resistant strain, 17e, was 430-fold resistant to fipronil in topical application bioassay and 23-fold resistant in feeding bioassay at LD50/LC50. We also tested the toxicity of fipronil in a feeding bioassay and gamma-HCH in topical application bioassay on thirteen housefly field populations. Eleven of the field populations had resistance factors for fipronil ranging from 0.98 to 2.4 at LC50, whereas two populations were 4.0- and 4.6-fold resistant to fipronil. The resistance level to gamma-HCH at LD50 in the field populations ranged from 1.8- to 8.1-fold. The two strains showing fipronil resistance were 3.4- and 8.1-fold resistant to gamma-HCH. Fipronil and gamma-HCH toxicities were positively correlated in the field populations. Biochemical assays of esterase, glutathione S-transferase and cytochrome P450 monooxygenase indicated that the low fipronil resistance observed in laboratory and field strains could be caused by elevated detoxification or be due to a target-site resistance mechanism with cross-resistance to gamma-HCH.
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PMID:Cross-resistance potential of fipronil in Musca domestica. 1538 4

The ability of mosquito larvae to tolerate toxic compounds (temephos, Bacillus thuringiensis var. israelensis, toxic vegetable leaf litter) was examined on a laboratory larval strain of Aedes aegypti L. Bioassays and detoxifying enzyme activity measurements were performed to compare tolerance/resistance capacities. The possibility of a functional plasticity of detoxifying equipment was investigated through experimental determination of the inductive effect of each xenobiotic within a given generation. In the same way, the selective effect of a toxic leaf litter was also investigated along successive generations. Results revealed that differential cytochrome P450 monooxygenase, esterase, and glutathione S-transferase activity levels correlated with the bioassay results. Both induction and selection increased larval tolerance to the xenobiotics used and increased the levels of larval detoxifying enzyme activities.
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PMID:Response of Aedes aegypti (Diptera: Culicidae) larvae to three xenobiotic exposures: larval tolerance and detoxifying enzyme activities. 1651 8

Sublethal effects of three pesticides including atrazine (triazine herbicide), DDT (organochlorinated insecticide), and chlorpyrifos (organophosphate insecticide) on acetylcholinesterase (AChE), general esterase (GE), glutathione S-transferase (GST), and cytochrome P450 monooxygenase (P450) activities were evaluated in the aquatic midge Chironomus tentans. Exposures of midges to atrazine at 30 and 150 micrograms per liter (microg/L) for 20 d (i.e., from the first- to fourth-instar larvae) enhanced P450 O-deethylation activity by 12.5- and 15.5-fold, respectively, but did not significantly change AChE, GST, and GE activities. Similar exposures to DDT at 0.01 and 0.05 microg/L did not significantly affect AChE, GE, and P450 activities; however, DDT at 0.05 microg/L enhanced GST activity toward the substrate 1-chloro-2, 4-dinitrobenzene by 33.6%. Exposures of midges to chlorpyrifos at 0.10 microg/L for 20 d reduced AChE activity by 59.8%, and GE activities toward the substrates alpha-naphthyl acetate and beta-naphthyl acetate by 30.7 and 48.8%, respectively. The reduced GE activities appear to be due to the inhibition of several esterases, particularly the one with a slow migration, by chlorpyrifos as demonstrated by non-denaturing polyacrylamide gel electrophoresis. Furthermore, exposure of midges to chlorpyrifos at 0.10 microg/L for 20 d enhanced the P450 O-deethylation activity by 3.3-fold although no significant effect was observed at 0.02 microg/L for the same enzyme. These results provide insights into the sublethal effects of these commonly detected pesticides in aquatic environments on important enzymes in aquatic midges.
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PMID:Sublethal effects of three pesticides on activities of selected target and detoxification enzymes in the aquatic midge, Chironomus tentans (diptera: chironomidae). 1686 2


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