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)

The effects of inhalation and cutaneous exposure to styrene on the drug metabolizing enzymes were studied in the rat. Rats were exposed eight hours per day, for seven successive days to 450 ppm concentration of styrene or received one cutaneous dose of styrene daily for seven consecutive days (0.5 and 3.0 g/kg). The animals were killed one day after the last dose. Styrene inhalation increased the activities of epoxide hydrase and UDPglucuronosyltransferase (4-methylumbelliferone as substrate) in liver (1.5- and 1.7-fold, respectively). Ethoxycoumarin deethylation was enhanced 1.7-fold in the kidney. The content of cytochrome P-450 in the liver and the activities of NADPH cytochrome c-reductase, benzpyrene hydroxylase and glutathione S-transferase in the liver and kidney were not altered. No changes in the enzyme activities were detected in the lung. Styrene depressed the epoxide hydrase activity in liver when administered cutaneously. No signs of enzyme induction could be seen after cutaneous administration.
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PMID:Effects of inhalation and cutaneous exposure to styrene on drug metabolizing enzymes in the rat. 62 79

Intoxication of male and female mice with a single dose (300 or 600 mg/kg) of 1,1,2,2-tetrachloroethane (TTCE) resulted in significant decreases in cytochrome P-450 (to 58-73% of the control) and NADPH-cytochrome (P-450) c-reductase (to 29-35% of the control) in hepatic microsomes. This was accompanied by an alteration of mixed function monooxygenases stemming from the marked reduction (to 20-64% of the control) of several oxidative activities to selected substrates towards different P-450 isozymes (classes IA1, IA2, IIB1, IIE1 and IIIA). As phase II markers, epoxide hydrolase (approximately 35% loss), UDP-glucuronosyl transferase (approximately 42% loss) and to a lesser extent glutathione S-transferase (approximately 17% loss) were all affected. Also, the activity of delta-aminolevulinic (ALA) synthetase was decreased (approximately 57% of the control). On the contrary, heme oxygenase activity was increased (up to 35%) at the maximal dose tested. The decrease of P-450-function may be explained in terms of an alteration in the rate of heme biosynthesis and degradation, provoking a loss of heme content (approximately 33%) as well as of the direct inactivation of both P-450 and reductase. Because of increasing evidence on the involvement of free radical intermediates in the case of toxicity of haloalkanes, electron spin resonance spectroscopy (ESR) spin-trapping in vivo techniques were used to characterize the possible free radical species involved in the observed liver damage. The results obtained with the spin-trap N-benzylidene-2-methylpropylamine N-oxide (phenyl t-butylnitrone, PBN) provide evidence for the formation and trapping of the CHCl2CHCl free radicals. The detection of conjugated diene signals by means of second-derivative spectrophotometry, have enabled us to show that in vivo lipid peroxidation may be one of the main mechanisms responsible for TTCE hepatotoxicity.
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PMID:On the hepatotoxicity of 1,1,2,2-tetrachloroethane. 131 68

The intrauterine position of rat fetuses between siblings of the same or opposite sex has been reported to alter sexually dimorphic behavioral and reproductive traits in the adult. The intrauterine fetal position of adult rats is identified by a three letter code as mMm (a male, M, located between two male siblings, m-m) and fFf (a female, F, positioned between two females, f-f). This study sought to determine whether intrauterine location affected the hepatic polysubstrate monooxygenase and glutathione S-transferase activity, plasma sex steroid levels and organ weights in adult Long-Evans rats. The hepatic microsomal cytochrome P-450 content was higher in females located in utero between two male littermates (mFm) than in females positioned between two females (fFf). NADPH cytochrome c reductase activity was higher in mMm males (positioned in utero between two males) than in fMf males (males contiguous to two female littermates) and female rats. Hepatic microsomal testosterone 2 alpha- and 6 beta-hydroxylase activity was undetectable in fFf female but both activities were measurable in mFm female rats. Testosterone 7 alpha-hydroxylase and 5 alpha-reductase activity was higher in females than in males, and higher in fFf than in mFm females. Glutathione S-transferase activity was not altered by fetal contiguity in male and female rats. Adult mMm males had a higher plasma testosterone level and relative gonadal weight, and lower plasma estradiol concentration than fMf males. The plasma progesterone concentration of fFf female was lower than that of mFm female rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intrauterine position on the hepatic microsomal polysubstrate monooxygenase and cytosolic glutathione S-transferase activity, plasma sex steroids and relative organ weights in adult male and female Long-Evans rats. 140 93

The c14CoS/c14CoS mouse has a homozygous deletion of about 1.2 cM on chromosome 7 that includes the albino (c) locus. The untreated 14CoS/14CoS newborn has been reported to exhibit a marked transcriptional activation of the hepatic NAD(P)H:menadione oxidoreductase (Nmo-1; DT diaphorase; quinone reductase; azo dye reductase) gene, as well as elevated UDP glucuronosyl-transferase (UGT1*06) and glutathione transferase (GT1) activities, when compared with the cch/cch wild-type and the cch/c14CoS heterozygote. We show here that the newborn hepatic activities of seven enzymes that play a role in the oxidative stress response--NMO1, UGT1*06, GT1, copper-zinc superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase--are increased 1.5- to 25-fold in 14CoS/14CoS, as compared with ch/ch and ch/14CoS mice. The activities of four additional enzymes having no known association with the oxidative stress response--benzo[a]pyrene hydroxylase (CYP1A1, cytochrome P(1)450), acetanilide 4-hydroxylase (CYP1A2, cytochrome P(3)450), lactate dehydrogenase (LDH), and NADPH-cytochrome c reductase--are not significantly different among the three genotypes. These data suggest that there exists an "oxidative stress" response in the untreated 14CoS/14CoS newborn. We postulate that a chromosome 7 regulatory gene, which we have named Nmo-1n, might encode a trans-acting negative effector of the Nmo-1 gene, and genes corresponding to the other elevated enzymic activities described above. When both copies of Nmo-1n are deleted, as is the case in 14CoS/14CoS mice, a battery of genes involved in oxidative stress is released from negative control and becomes activated--despite the absence of any apparent oxidative insult by foreign chemicals.
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PMID:"Oxidative stress" response in liver of an untreated newborn mouse having a 1.2-centimorgan deletion on chromosome 7. 154 Jan 61

Studies were undertaken to investigate the effect of t-butylated hydroxytoluene (BHT) on reduced glutathione (GSH) levels and related enzymes in rat ocular tissues. GSH levels were significantly enhanced when 1 microM BHT was included in the medium of rat lens cultures. BHT had a dose-dependent effect on GSH levels of lenses in cultures. Inclusion of 10 microM BHT in the culture medium resulted in a twofold increase in GSH levels of the lens within 24 hr. Increased gamma-glutamylcysteine synthetase activity concomitant with the increased amount of [35S]methionine incorporation in GSH strongly suggested that BHT caused enhanced levels of GSH in lenses by increasing de novo biosynthesis. A significant increase was also observed in glutathione S-transferase (GST) levels of lenses in culture containing BHT in the medium. Present studies also demonstrated that rat lens expresses only the mu and pi class GST isoenzymes and both these classes of isoenzymes were elevated by BHT. Oral administration of BHT to rats also resulted in enhanced in vivo levels of GSH in lens, retina and cornea. In addition, a significant in vivo increase in the levels of GST, GSH-peroxidase, GSH-reductase, gamma-glutamylcysteine synthetase, and glucose 6-phosphate dehydrogenase was observed in the lens, retina, and cornea of BHT-fed rats.
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PMID:t-butylated hydroxytoluene enhances intracellular levels of glutathione and related enzymes of rat lens in vitro organ culture. 154 39

Previously sedentary men (n = 23) and women (n = 18) were trained to run a half marathon contest after 40 weeks. Total blood glutathione had increased by 20 weeks of training and had returned to normal after 40 weeks. Erythrocyte glutathione reductase activity had increased by 20 weeks and remained elevated after 40 weeks. This effect was accompanied by decreases in glutathione reductase coefficients, which indicated that increases in the presence of riboflavin may have been responsible for the changes in reductase activity. Erythrocyte glutathione S-transferase activity had increased slightly after 20 weeks of training and a much more marked increase was found after 40 weeks. This may have been indicative of the occurrence of lipid peroxidation in this phase of training. The participants ran a 15-km race after the first 20 weeks of training and a half marathon after 40 weeks. Blood glutathione tended to decrease after the 15-km race and increased after the half marathon. In both cases it had returned to normal values 5 days after the race. Erythrocyte glutathione reductase was elevated 1 day after the races, and had returned to normal after 5 days. This could also have been explained from concurrent changes in the riboflavin content of the erythrocytes. Erythrocyte glutathione S-transferase activity decreased after both races, but was restored 5 days after the half marathon while such was not the case after the 15-km race.
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PMID:Changes in blood glutathione concentrations, and in erythrocyte glutathione reductase and glutathione S-transferase activity after running training and after participation in contests. 159 62

The age-courses of concentrations of reduced (GSH) and oxidized (GSSG) glutathione, of GSH synthesizing enzyme activities, of glutathione S-transferase (GST), of GSSG-reductase (GR) and of biliary GSH and GSSG export were measured in livers from male Uje:WIST rats. Additionally, the age-courses of plasma GSH and GSSG concentrations were investigated. The hepatic level of GSH showed a biphasic pattern with a first maximum immediately after birth and a small second peak at the 50th day of life. The GSSG level increased continuously up to day 60 of life. The cytosolic GSH synthesizing enzyme activities showed diverse developmental patterns indicating different regulation principles. The hepatic activity of GR was relatively constant in the different age groups after birth. The GST activity (with o-dinitrobenzene as substrate) was relatively low at birth (about 30% of the maximum measured at day 60 of life). The maximum of GSH plasma level was found at birth. With increasing age a significant decrease in this level was observed. The excretion rate of total GSH (GSH + 2 GSSG) in bile was found to increase about 9-fold between 15 and 105 days of age. The results indicate that changes of hepatic GSH concentration with age are dependent on numerous factors. The balance between synthesis, catabolism and export is important for the maintenance of this level.
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PMID:Ontogenetic changes in hepatic glutathione system (synthesis, catabolism, export) of male Uje:WIST rats. 179 40

By the use of ANS(1-anilinonaphthalene-8-sulfonate) and DPH(1, 6-diphenyl-1, 3, 5-hexatriene) as fluorescent probes, correlation between liver microsomal membrane fluidity and drug metabolizing enzyme activity has been studied in rats. phenobarbital(PB) ip treatment caused an increase in P-450 content, cytochrome C reductase.aminopyrine N-demethylase(AMD) and glutathione S-transferase(GST) activities by 78, 66, 270 and 52%, respectively. However, there was a simultaneous decrease in microsomal membrane fluorescent intensity and microviscosity, i.e. an increase in membrane fluidity. There is a positive linear correlation between microsomal membrane fluidity and cytochrome C reductase and AMD activities (r = 0.798, r = 0.781, respectively, P less than 0.05). This result suggests that there may be some relationship between microsomal membrane fluidity and drug-metabolizing enzymatic activities in PB-treated rats.
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PMID:[Studies on correlation between liver drug metabolizing enzyme activities and microsomal membrane fluidity in phenobarbital treated rats]. 180 18

Aflatoxin B1 (AFB1) appears to be a risk factor for upper respiratory tumors in individuals occupationally exposed to AFB1-contaminated grain dusts. To study the potential effects of this mycotoxin in the upper airways, the metabolism of AFB1 was investigated in tracheal cultures and purified tracheal microsomes from rabbit, hamster and rat. These species differ in the proportion of P450-containing non-ciliated epithelial (NC) cells in the upper airway (17, 41, 0% respectively). Cultures from the rabbit produced the highest level of the AFB1 metabolites AFB1-dihydrodiol (AFB1-diol), GSH-AFB1, AFM1, AFB2a and the highest tracheal microsomal pentoxyresorufin-O-dealkylase (PROD) activity (an indicator of that P450 activity which activates AFB1) and greater cytosolic GSH-transferase activity compared to hamster and rat. Tracheal microsomal epoxide hydrolase activity, AFB1-diol production, cytochrome P450 content, P450 reductase and ethoxyresorufin-O-dealkylase (EROD) activity (an indicator of AFB1 detoxification) were highest in the hamster. Although the overall metabolic activity in rat tracheal epithelium was low, PROD-related activity appeared to predominate. Conjugation with GSH was the major detoxification pathway in rabbit and rat upper airways, although levels of AFB1-GSH and activities of glutathione transferase were significantly lower in the rat than in the rabbit and hamster. Hydrolysis of the putative AFB1-2,3-epoxide via epoxide hydrolase appeared to be the major AFB1 detoxification pathway in hamster tracheal epithelium as indicted by corresponding high tracheal microsomal AFB1-diol production and EH activity compared to rabbit and rat. Glucuronide and sulfate conjugates of AFB1 and its metabolites were formed in tracheal explant cultures from these three species, although amounts formed were minor. These results indicate that rabbit upper airway epithelium contains metabolic activity primarily involved in AFB1 activation, whereas AFB1 detoxification pathways predominante in hamster. Furthermore, the characteristics of carcinogen metabolism are not predictable based solely on airway morphology.
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PMID:Comparative biotransformation of aflatoxin B1 in mammalian airway epithelium. 189 9

The use of Aroclor 1254 to induce S9 liver fractions is a standard method for conducting short-term genotoxicity assays. An alternative induction procedure, using beta-naphthoflavone (beta-NF), as a safe (non-carcinogenic) substitute for polychlorinated biphenyls, combined with sodium phenobarbital (PB), was found to be equally effective. The aim of this work is to realize a novel schedule of induction for the preparation of metabolizing systems containing a wider spectrum of induced cytochrome P450s. Five inducers of different 'classes' such as PB (class IIB P450s), beta-NF (IA), isosafrol (IA2), ethanol (IIE1) and pregnenolone 16 alpha-carbonitrile (IIIA) were injected daily both separately (to achieve maximal monooxygenase induction) in male and female mice. Induction was monitored using specific P450-linked activities. In the optimal schedule for complete induction, the various monooxygenases were greater (2- to 4-fold) than those achieved by the classical schedule. More than a 14-fold increase of total P450 and 3.3-fold increase of NADPH-cytochrome (P450) c-reductase activity, over those uninduced, account for the above increase. For example, there was a marked increase in the deethylation of ethoxyresorufin (37-fold) compared to the uninduced mice that was considerably higher than classical induction (8-fold over uninduced). On the contrary, phase II reactions i.e. epoxide hydrolase, glutathione S-transferase, glutathione S-epoxide transferase and UDP-glucuronosyl transferase, examined to compare the phase I/phase II ratios in the traditional and proposed procedures, were increased to a lesser extent (2-fold over uninduced). No significant sex differences were seen. Five precarcinogens specifically metabolized by each of the induced P450s elicited a higher mutagenicity response in the presence of superinduced fractions with respect to the classical one, when tested on Salmonella typhimurium (cyclophosphamide, benzo[alpha]pyrene, 2-naphthylamine and dimethylnitrosamine) or Saccharomyces cerevisiae D7 strain (diethylstilbestrol). These novel metabolizing biosystems, with an enhanced spectrum of induced P450s and oxidative/post-oxidative reaction rates, are recommended for detecting unknown xenobiotics in genotoxicity studies.
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PMID:Wide spectrum detection of precarcinogens in short-term bioassays by simultaneous superinduction of multiple forms of cytochrome P450 isoenzymes. 190 89


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