Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:7732-18-5 (water)
 694,341 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetonitrile (AN) and seven of its halogenated derivatives known to be water disinfectant by-products were evaluated for their action on hepatic cytosolic glutathione S-transferase (GST) activity using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. Increasing concentrations of acetonitrile, monofluoroacetonitrile (MFAN), monochloroacetonitrile (MCAN), and monobromoacetonitrile (MBAN) up to 10 mM failed to produced 50% inhibition of the activity of GST enzyme. However, dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), dibromoacetonitrile (DBAN), and monoiodoacetonitrile (MIAN) were potent inhibitors with 150 values of 2.49, 0.34, 0.82, and 4.44 mM, respectively. At concentrations equivalent to their 150, MIAN, DCAN, and DBAN decrease both apparent Km and Vmax of the enzyme activity toward glutathione (GSH) to 20-50% of control. TCAN significantly increases both apparent Km and Vmax for GSH to 650 and 120% of control values, respectively. The inhibitory effect of haloacetonitriles (HAN) on hepatic GST activity toward CDNB was found to be a mixed type. The inhibitory effect of DCAN, DBAN, and TCAN on the hepatic GST activity was found to be reversible and the activity was completely recovered after dialysis of the inhibited enzyme. MIAN, however, inhibited GST activity in an irreversible manner. Haloacetonitriles' induced inhibition of hepatic GST activity in vitro is consistent with that observed in vivo. The data presented in this study show that haloacetonitriles induced reversible inhibition of hepatic GST activities, and this effect may lead to decreased detoxification of other electrophilic chemicals.
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PMID:Studies on the mechanism of haloacetonitriles toxicity: inhibition of rat hepatic glutathione S-transferases in vitro. 278 58

The gene expression of liver major gap junction (GJ) protein was studied in rats systemically administered phenobarbital, a rat liver tumor promoter. Using a GJ protein cDNA and northern blot analysis, the level of GJ protein mRNA in liver was observed to be markedly reduced at 4 and 11 wk of phenobarbital exposure (0.1% in drinking water). However, the level of GJ protein mRNA was not altered in kidney at 11 wk of exposure. In liver, phenobarbital did not induce expression of the neoplasm-associated marker genes glutathione S-transferase (placental form) and gamma-glutamyltranspeptidase, while in kidney the observed expression of these genes was not changed. These in vivo results indicate that phenobarbital reduces GJ protein gene expression specifically in rat liver without altering expression of genes often altered during liver carcinogenesis, and they support assigning a role for the impairment of gap junctional intercellular communication in phenobarbital-mediated liver tumor promotion.
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PMID:Phenobarbital specifically reduces gap junction protein mRNA level in rat liver. 285 4

The values of the immunohistochemical demonstrations of glutathione S-transferases (GSTs) A, B, C and P and histochemical demonstrations of gamma-glutamyl transpeptidase (gamma-GT) for detection of enzyme altered foci in F344 rat liver were compared. Rats were given a single i.p. injection of 200 mg/kg body weight of diethylnitrosamine (DENA), from 2 weeks later they were given 0.02% N-2-fluorenylacetamide (2-FAA), phenobarbital (PB), butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) in their diet for 6 weeks and then they were given basal diet and tap water for 4 weeks. They were subjected to partial hepatectomy at the end of week 3. Results showed that immunohistochemical demonstration of GSTs A, B and C for detection of foci were only effective when the administration of 2-FAA, PB, BHA or BHT in the diet was discontinued, because these GSTs were induced in surrounding hepatocytes by these compounds in the diet. gamma-GT was induced in periportal hepatocytes strongly by BHA and BHT and slightly by PB, and gamma-GT positive foci in periportal areas were not distinguishable from gamma-GT positive periportal hepatocytes. GST-P was also induced moderately by BHA and slightly by BHT in periportal hepatocytes, but all GST-P positive foci were clearly distinguishable. In addition, almost all gamma-GT positive foci gave a positive reaction for GST-P, but 5-10% of the GST-P positive foci were not gamma-GT positive.
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PMID:Relative merits of immunohistochemical demonstrations of placental, A, B and C forms of glutathione S-transferase and histochemical demonstration of gamma-glutamyl transferase as markers of altered foci during liver carcinogenesis in rats. 286 13

Glutathione S-transferase in the cytosol of rainbow trout liver was partially purified by affinity chromatography on a column with glutathione coupled to epoxy-activated Sepharose 6B, which retained 94% of the total activity. Chromatofocussing on a Polybuffer exchanger 118 column separated the glutathione S-transferase into six major cationic isoenzymes (K1-K6), and some minor fractions. SDS-polyacrylamide slab gel electrophoresis showed K1-K3 to be heterodimers with subunits of Mr 25,000 and 26,500, and K4-K6 to be homodimers with subunits of Mr 25,000. The glutathione S-transferase isoenzymes were partially characterized by different biochemical parameters. The hepatic rainbow trout glutathione S-transferases were inhibited by the organic water pollutants, 1,4-benzoquinone and 2,4-dichlorophenoxyacetic acid. The same kinetic inhibition patterns were observed with these inhibitors as for rat liver glutathione S-transferases. It is concluded that rainbow trout glutathione S-transferases can play a key role in the detoxication of organic micropollutants in the aquatic environment.
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PMID:Hepatic glutathione S-transferases in rainbow trout and their interaction with 2,4-dichlorophenoxyacetic acid and 1,4-benzoquinone. 286 27

The multipotential carcinogen N,N'-dibutylnitrosamine (DBN) was given to F344 male rats for 2 weeks at three dose levels to study the concentration dependence of its organ specificity. Groups of 20 rats were given water containing 0.25, 0.125 or 0.063% DBN for 2 weeks and then tap water only to drink until they were killed 52 weeks after the start of the experiment. DBN induced preneoplastic lesions in the liver, esophagus, forestomach and urinary bladder. Carcinoma was found only in the liver. Induction of preneoplastic focal hepatocyte lesions positive for the P-form of glutathione S-transferase (GST-P) was quantitatively dependent on the dose of DBN. In the urinary bladder, the incidences of papillary or nodular hyperplasia (PNH) and papilloma of transitional cells tended to increase at higher doses. The incidence and number per unit length of basal cell-type hyperplasias of the esophageal epithelium were significantly higher in all DBN groups than in the control group, through the increase did not show a clear dose-dependency. The incidence of epithelial basal cell hyperplasia of the forestomach was significantly increased at all doses and the increase was apparently dose-related. These results indicate that even in a short-term experiment, DBN exerted multipotential carcinogenic effects. Thus, this system could be used for assay of the modifying effects of compounds administered subsequently on carcinogenesis in different organs.
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PMID:Induction of tumors in the liver, urinary bladder, esophagus and forestomach by short-term treatment with different doses of N,N'-dibutylnitrosamine in rats. 288 67

Immunohistochemical staining using anti-rat glutathione S-transferase placental form (GST-P) rabbit antibody and enzyme histochemical staining for gamma-glutamyltranspeptidase (gamma-GT) were investigated in lesions appearing during lung carcinogenesis induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Rats were given BHP at a concentration of 2000 p.p.m. in drinking water, and were killed after 12 weeks of BHP intake, after 12 weeks of BHP intake followed by 12 weeks of tap water intake or after 20 weeks of continuous BHP intake. It was found that bronchiolo-alveolar hyperplasias, adenomas, adenocarcinomas, squamous metaplasias and squamous cell carcinomas had been induced by BHP. All of the squamous metaplasias and squamous cell carcinomas were shown to stain with GST-P but not with gamma-GT. On the other hand, the hyperplasias, adenomas and adeno-carcinomas stained with gamma-GT to various degrees and in different areas, but did not stain with GST-P. The incidence of gamma-GT phenotype and the average percentage of gamma-GT-positive areas in hyperplasias and adenomas suggested that adenocarcinomas might develop from hyperplasias and adenomas. These results suggest that GST-P is a marker for squamous lesions while gamma-GT is a marker for adenomatous lesions in rat lung carcinogenesis. Furthermore, squamous metaplasias appear to be preneoplastic lesions of squamous cell carcinomas while gamma-GT-positive hyperplasias or adenomas are preneoplastic lesions of peripheral adenocarcinomas.
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PMID:Comparative histochemical investigation of the glutathione S-transferase placental form and gamma-glutamyltranspeptidase during N-nitrosobis(2-hydroxypropyl)amine-induced lung carcinogenesis in rats. 289 57

1. The effect of an acute testicotoxic dose of cadmium (CdCl2.H2O, 2.0 mg/kg i.p.) on liver morphology and drug-metabolizing enzyme activities were studied in adult male and female rats. 2. Cd treatment to female rats caused a slight and reversible decrease in hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and aminopyrine N-demethylase (APND) activities. 3. No significant changes were noted in the liver morphology, serum alanine aminotransferase activities, enzyme induction by phenobarbital and 3-methylcholanthrene, and glucuronosyl-transferase (GT) and glutathione S-transferase (GST) activities. 4. The same Cd treatment to male rats, however, resulted in a much more pronounced and prolonged reduction in AHH and APND activities, which was attributable to a Cd-induced testicular necrosis and, hence, impairment of androgen secretion. 5. Accordingly, Cd treatment to castrated male rats did not lower the enzyme activities any further, and full recovery of activities was obtained after the administration of testosterone. 6. Both GT and GST, the two sex-independent enzymes, were not significantly affected by either Cd or gonadectomy in the male rat. 7. The present data show that a low acute dose of Cd induces chemical castration without severely altering hepatic function.
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PMID:Effects of a testicotoxic dose of cadmium on the liver and drug metabolism in the rat. 289 6

Mice of the strain WEHI 129/J are genetically resistant to chronic Schistosoma mansoni infection. Resistance is expressed in at least 50% of mice, with the remaining mice showing normal susceptibility to infection. The serum antibody specificities in the resistant proportion of WEHI 129/J were analyzed at various times after exposure to cercariae by using both Western blotting and immunoprecipitation. Comparisons with the susceptible proportion of WEHI 129/J and other permissive mouse strains revealed four antigens that were differentially recognized by resistant mice at various times of infection: Sm25, an Mr 25,000 integral membrane protein of adult worms that was better recognized by resistant mice 40 to 50 days after exposure; Sm67, an Mr 67,000 water-soluble antigen of adult worms that was better recognized by resistant mice at days 30 to 40; Sm120, an Mr 120,000 antigen expressed by cercariae and adult worms that was differentially recognized, although inconsistently, at days 20 to 40 postexposure; and Sm26, an Mr 26,000 glutathione S-transferase that was uniquely recognized by resistant mice at day 20 in two of three experiments. Analysis of antibody specificities in (BALB/c x WEHI 129/J)F1 x WEHI 129/J backcross mice indicated that high responsiveness to Sm25 at days 40 to 50 correlated with resistance. The candidacy of these four molecules as vaccines for schistosomiasis mansoni is discussed.
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PMID:Schistosoma mansoni antigens differentially recognized by resistant WEHI 129/J mice. 313 67

Hepatic GSH conjugation is the initial step in the mammalian biotransformation of hexachloro-1,3-butadiene (HCBD) and analogous haloalkenes. The present paper reports an in vitro investigation of the glutathione-dependent conversion of HCBD to water-soluble products, i.e. the enzyme-catalyzed conjugation of HCBD with GSH. The method employed avoids artifacts due to the volatility, low solubility and hydrophobic nature of the chloro-carbon substrate. In order to assess the relative importance of membrane-bound and cytosolic glutathione S-transferase in the conjugation process, microsomal and cytosolic fractions from adult rat liver were tested separately for their ability to promote water solubilisation of the substrate. In addition, microsomal purified and liposomally reconstituted glutathione S-transferase, were tested. The reaction exhibited Michaelis-Menten kinetics, and conjugation rates were linear for at least 20 min. The hepatic microsomal fraction metabolized HCBD 116 times faster than the cytosolic fraction when substrate saturated. Both mono- and bis-substituted conjugates were formed by microsomal as well as by the cytosolic fraction. Treatment of animals with inducers and the use of specific inhibitors indicated absence of cytochrome P-450 involvement in the formation of water soluble HCBD metabolites and supported the view that microsomal glutathione S-transferase is more important in catalyzing GSH conjugation of this haloalkene than the cytosolic forms of transferases.
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PMID:Features of microsomal and cytosolic glutathione conjugation of hexachlorobutadiene in rat liver. 320 1

Brain trauma was induced in rats by impact of a steel bar on the head with a force such that damage (as measured by neurological scoring) was reversible in fourteen days. Systemic treatment (intraperitoneal injections) with free bovine copper superoxide dismutase or a liposomal form of the enzyme considerably shortened recovery time to less than half. Tests included cranial nerves--cornean and aural reflexes, and sensorial motricity functions--gripping reflexes, displacement reactions, recovery and flexion reflexes, equilibrium tests and spontaneous mobility. Normalisation of EEG recordings was also greatly accelerated in the case of treated animals. No changes of brain glutathione peroxidase, glutathione transferase or Mn superoxide dismutase in traumatized animals were observed. However a slight decrease in Cu-SOD occurs. Cerebral lipoperoxidation is increased in the traumatized animals compared with controls. This increase is reduced on treatment of the rats with liposomal SOD (or the free enzyme). Very small amounts of the exogenous SOD pass the brain barrier, the permeability of which is increased in traumatized animals. The enzyme is particularly concentrated in the cortex. Despite apparent total neurological recovery at 15 days for untreated traumatized animals, significant differences in EEG recordings, in percentage cerebral water content and in histological examination of brain tissue of these controls compared with treated animals were observed with a net improvement in the latter case. The results obtained with this model suggest that clinical treatment of coma states and brain traumas with liposomal superoxide dismutase may have certain advantages over orthodox treatments.
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PMID:Treatment of brain trauma with liposomal superoxide dismutase. 322 60


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