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Query: CAS:7732-18-5 (water)
 694,341 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Subchronic treatment of male and female rats with CCl4 (0.2 ml/kg orally twice weekly) and drinking water containing 5% ethanol for four weeks led to a 20 to 40-fold increase in serum sorbitol dehydrogenase activity and to an augmentation of the liver triglyceride and hydroxyproline contents, indicating steatosis and fibrosis, respectively. Liver fibrosis was less pronounced in females than in male rats. 2. As a consequence of these alterations the hepatic microsomal mixed-function oxidase activity as measured by aminopyrine demethylation was decreased with concomitant loss of cytochrome P-450 in both sexes. Aniline hydroxylation as well as the activity of the NADPH-cytochrome c reductase showed no significant alterations. 3. While the hepatic glutathione content remained unchanged, the cytosolic glutathione S-transferase activities towards both an aryl and an epoxide substrate were markedly decreased following the development of liver fibrosis both in male and female rats.
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PMID:Effect of carbon tetrachloride--alcohol-induced liver fibrosis on microsomal mixed-function oxidases and the cytosolic glutathione-conjugating system in rat liver. 685

Glutatione transferases (RX:glutathione R-transferases, EC 2.5.1.18) B and AA were purified from rat liver to investigate the mechanism for their apparent GSH peroxidase activity (GSSG formation). Both transferases catalyze an overall reaction in which loss of cumene hydroperoxide is accompanied by a stoichiometric increase in GSSG. Inclusion of cysteamine, a thiol, results in a reduction of GSSG formation but has no effect on hydroperoxide loss. Cysteamine does not inhibit the transferase-catalyzed conjugation of GSH and 1-chloro-2,4-dinitrobenzene. Peroxidase reactions carried out in the presence of cyanide, another nucleophile, also result in a reduction of GSSG formation without altering the rate of cumene hydroperoxide loss; cyanide does not inhibit transferase activity with 1-chloro-2,4-dinitrobenzene. Both cysteamine and cyanide are capable of blocking GSSG formation in the non-enzymic oxidation of GSH by hydrogen peroxide without blocking H2O2 loss. These results are consistent with a mechanism for GSH transferases in which nucleophilic attack by GS- on hydroperoxide results in a reactive intermediate, presumably the sulfenic acid of glutathione, GSOH. GSH + ROOH in equilibrium GSHO + ROH (1) This sulfenic acid then reacts non-enzymically with GSH to produce GSSG. GSOH + GSH in equilibrium GSSG + H2O (2) The summing of Reactions 1 and 2 explains the observed stoichiometry. Cysteamine and cyanide can compete with GSH for the sulfenic acid in Reaction 2, thus reducing GSSG formation. Thios.
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PMID:The glutathione peroxidase activity of glutathione S-transferases. 735 Sep 21

The modifying potential of prior administration of toxic agents was investigated in our multi-organ carcinogenesis model using male F344/DuCrj rats with the aim of assessing the link between tissue damage and initiation. Animals were administered one of four toxic agents for 8 wk, and then treated with N-diethylnitrosamine (DEN, 100 mg/kg body weight (b.w.), intraperitoneally (i.p.), single injection), N-methylnitrosourea (MNU, 20 mg/kg b.w., i.p., four times during wk 9 and 10), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking water, during wk 11 and 12) for multi-organ carcinogenesis. All surviving rats were killed at the end of wk 36, and the major organs carefully examined for preneoplastic and neoplastic lesion development. Immunohistochemical demonstration of glutathione S-transferase placental form (GST-P) positive foci was also performed to facilitate quantitative assessment of liver lesion development. D-galactosamine (300 mg/kg b.w., i.p., once a week), a hepatotoxin, significantly inhibited the induction of GST-P positive foci, while 4,4'-diaminodiphenylmethane (DDPM, 0.1% in diet), a bile duct proliferator which is itself a hepatocarcinogen, possessed enhancing activity. DDPM, also a goitrogen, clearly inhibited the development of follicular cell tumors in the thyroid. Uracil (3.0% in diet), which is an inducer of papillomatosis in the urinary bladder, did not exert any enhancing potential on bladder carcinogenesis. Bleomycin (2 mg/kg b.w., i.p., twice a week), which is an alveolar epithelium injuring agent, also did not modify the induction of alveolar epithelium proliferative lesions. These results indicate that prior organ injury by toxic agents does not always act to enhance sensitivity to carcinogenesis.
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PMID:Modifying influence of prior treatment with toxic agents on induction of preneoplastic and neoplastic lesions in a medium-term multi-organ carcinogenesis bioassay. 750 56

Effects of hepatocyte growth factor were investigated in a two-stage rat liver carcinogenesis protocol. Male F344 rats were first treated with diethylnitrosamine (200 mg/kg, i.p.) and then, starting two weeks later, with N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 6 weeks at a dose of 0.01% in drinking water. Hepatocyte growth factor, which was injected i.v. at a dose of 200 micrograms/kg body weight one (at week 3) or two times (at weeks 3 and 4) during EHEN administration, significantly increased the development of preneoplastic glutathione S-transferase placental form-positive foci. Although the observed effects of hepatocyte growth factor were weaker than that of the two-thirds partial hepatectomy (PH) performed at week 3, the present results suggest that the enhancing effects of PH performed during the promotion stage may be largely mediated through induction of hepatocyte growth factor.
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PMID:Hepatocyte growth factor enhancement of preneoplastic hepatic foci development in rats treated with diethylnitrosamine and N-ethyl-N-hydroxyethylnitrosamine. 755 93

The ligand-binding domain of the low-density lipoprotein receptor comprises seven cysteine-rich repeats, which have been highly conserved through evolution. This domain mediates interactions of the receptor with two lipoprotein apoproteins, apo E and apo B-100, putatively through a calcium-dependent association of the ligands with a cluster of acidic residues on the receptor. The second repeat (rLB2) of the receptor binding domain has been expressed as a thrombin-cleavable GST fusion protein, cleaved, and purified. On oxidation the protein refolded to give a single peak on reverse-phase HPLC. The aqueous solution structure of rLB2 has been determined using two-dimensional 1H NMR spectroscopy. In contrast to the amino-terminal repeat, rLB1, rLB2 has a very flexible structure in water. However, the conformation of rLB2 is markedly more ordered in the presence of a 4-fold molar excess of calcium chloride; the proton resonance dispersion and the number of NOESY cross-peaks are greatly enhanced. The three-dimensional structure of rLB2, obtained from the NMR data by molecular geometry and restrained molecular dynamics methods, parallels that of rLB1, with an amino-terminal hairpin structure followed by a succession of turns. However, there are clear differences in the backbone topology and structural flexibility. As for rLB1, the acidic residues are clustered on one face of the module. The side chain of Asp 37, which is part of a completely conserved SDE sequence thought to be involved in ligand binding, is buried, as is its counterpart (Asp 36) in rLB1. These results provide the first experimental support for the hypothesis that each of the repeats in the ligand-binding domain has a similar global fold but also highlight significant differences in structure and internal dynamics.
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PMID:Three-dimensional structure of the second cysteine-rich repeat from the human low-density lipoprotein receptor. 757 52

Insects possess a suite of antioxidant enzymes and small molecular weight antioxidants that may form a concatenated response to an onslaught of dietary and endogenously produced oxidants. Antioxidant enzymes such as superoxide dismutase, catalase, glutathione transferase, and glutathione reductase have been characterized in insects. Water-soluble and lipid-soluble antioxidants such as ascorbate, glutathione, tocopherols, and carotenoids have not been well studied in insects but may play very important antioxidant roles. Additionally, the peritrophic matrix and trehalose may possess important antioxidant functions in insects. The enzymatic recycling of ascorbate, first noted in green plants, may also exist in insects. A greater understanding of these antioxidant systems may provide greater understanding about the ecological relationships of insects with their hosts.
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PMID:Antioxidant systems in insects. 760 43

The potential usefulness of an insect model to evaluate oxidative stress induced by environmental pollutants was examined with trivalent arsenic (As3+, NaAsO2) and pentavalent arsenic (As5+, Na2HAsO4) in adult female house flies, Musca domestica, and fourth-instar cabbage loopers, Trichoplusia ni. M. domestica was highly susceptible to both forms of arsenic following 48 h exposure in the drinking water with LC50s of 0.008 and 0.011% w/v for As3+ and As5+, respectively. T. ni larvae were susceptible to dietary As3+ with an LC50 of 0.032% w/w but seem to tolerate As5+ well with an LC50 of 0.794% concentration after 48 h exposure. The minimally acute LC5 dose of both As3+ and As5+ varied considerably but averaged 0.005% for both insects. The potential of both valencies of arsenic for inducing oxidative stress in the insects exposed ad libitum to approximately LC5 levels was assessed. The parameters examined were the alterations of the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), the peroxidase activity of glutathione transferase (GSTPX), and glutathione reductase (GR), and increases in lipid peroxidation and protein oxidation. SOD (1.3-fold), GST (1.6-fold), and GR (1.5-fold) were induced by As3+ in M. domestica but CAT and GSTPX were not affected. As5+ had no effect on M. domestica. In T. ni, the antioxidant enzyme activities were not affected by As3+ except for SOD which was suppressed by 29.4% and GST which was induced by 1.4-fold. As5+ had no effect except the suppression of SOD by 41.2%. Lipid peroxidation and protein oxidation, which represent stronger indices of oxidative stress, were elevated in both insects by up to 2.9-fold. However, based on the antioxidant enzyme response to the arsenic anions, the mode of action of arsenic induced oxidative stress may differ between the two insects. Until this aspect is further clarified, evidence at this time favors the prospect of As3+ as a pro-oxidant, especially for M. domestica.
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PMID:An insect model for assessing oxidative stress related to arsenic toxicity. 760 44

The acute combined effects of cadmium (Cd) and nickel (Ni) on hepatic monooxygenase activities (ethylmorphine N-demethylase, EMND; aminopyrine N-demethylase, AMND; aniline 4-hydroxylase, AH), cytochrome P-450, cytochrome b5, microsomal heme and reduced glutathione (GSH) levels and glutathione S-transferase (GST) activities toward several substrates (1-chloro-2,4-dinitrobenzene, CDNB; 1,2-dichloro-4-nitrobenzene, DCNB; ethacrynic acid, EAA; 1,2-epoxy-3-(p-nitrophenoxy)-propane, ENPP) were determined and compared with those of Cd or Ni alone in mice. Male adult mice (25-30 g) were administered either a single dose of Cd (3.58 mg CdCl2.H2O/kg, i.p.) 48 hr prior to killing or a single dose of Ni (59.5 mg NiCl2.H2O/kg, s.c.) 16 hr prior to killing. For the combined treatment, the animals received the single dose of Ni 32 hr after the single dose of Cd and were then killed 16 hr later. Cd treatment alone significantly decreased EMND, AMND, and AH activities and cytochrome P-450 and heme levels as compared with controls. Cytochrome b5 level was not altered by Cd treatment. Cd also inhibited GSH level and the GST activities toward CDNB, EAA and ENPP significantly. No significant change was observed in the GST activity for DCNB by Cd. Ni treatment alone, however, decreased the monooxygenase and GST activities studied, and cytochrome P-450, cytochrome b5, heme and GSH levels significantly. Combined treatment significantly depressed the monooxygenase activities and cytochromes and heme levels. GSH level was not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential responses of hepatic monooxygenases and glutathione S-transferases of mice to a combination of cadmium and nickel. 765 85

The metabolism of 1,2-dibromo-3-chloropropane (DBCP), measured as the formation of water soluble metabolites and metabolites covalently bound to macromolecules, was studied in isolated rat liver, kidney, and testicular cells, in subcellular fractions, and with purified rat and human glutathione S-transferases (GSTs). The rate of formation of water soluble metabolites in the cells were in the order liver > kidney > testis. The rate of covalent macromolecular binding of reactive DBCP metabolites in the different cell types was of the same relative order. Pretreatment of the cells with the GSH depleting agent diethyl maleate (DEM) markedly decreased the rate of covalent binding in all cell types. Both the overall metabolism and the formation of DBCP metabolites that covalently bound to macromolecules, were substantially higher in rat testicular cells compared to hamster testicular cells. Rat liver cytosol and microsomes, and various purified rat and human GSTs extensively metabolized DBCP to water soluble metabolites in the presence of GSH. When compared to isolated cells, substantially lower rates of binding per mg protein could be observed in subcellular fractions. Binding of DBCP was detected in the microsomal and cytosolic fractions in the absence of NADPH, though in microsomes fortified with a NADPH-regenerating system, the generation of reactive DBCP metabolites was approximately doubled. Studies with purified rat GST isozymes showed that the relative overall GSH conjugation activity with DBCP was in the following order: GST form 3-3 > 2-2 approximately 12-12 > 1-1 > 4-4 approximately 8-8 approximately 7-7. Furthermore, human GST forms also readily metabolized DBCP with activities of GST A1-2 > A2-2 approximately A1-1 > M1a-1a > M3-3 approximately P1-1.
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PMID:Metabolism of 1,2-dibromo-3-chloropropane by glutathione S-transferases. 767 43

The skin is the major environmental interface of the human body and is repeatedly exposed to a broad array of exogenous chemicals potentially capable of causing toxicity. In the present study we have applied 3, 6 or 12 ml leaded gasoline/kg body weight to the skin of adult male Swiss mice for 7 consecutive days and then sacrificed the animals on 8th day after an overnight fast. Glutathione (GSH) concentration, lipid peroxidation and other GSH-dependent enzyme activities were measured in skin, liver, brain and blood tissues of the mice. Topical application of 12 ml/kg gasoline caused a significant increase in water consumption by the animals, although, their body weight and food consumption was not significantly affected. A 40-60% decrease in blood concentration of glucose, triglyceride, and cholesterol was also observed after the treatment. The hemoglobin concentration, GSH content, lipid peroxidation and glucose 6-phosphate dehydrogenase activity of erythrocytes were not significantly affected by the gasoline treatment. However, a decrease in GSH concentration (16-21%), lipid peroxidation (30-60%) and glutathione S-transferase (GST) activity (30-40%) was observed in skin, liver and brain after gasoline application. Western blot analysis of tissues using antibodies against GST isoenzymes demonstrated an alteration in the expression of various GST isoenzymes after gasoline treatment. Our results suggest that topical exposure of gasoline causes some deleterious effects on skin and extracutaneous tissues.
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PMID:Alteration of glutathione, glutathione S-transferase and lipid peroxidation in mouse skin and extracutaneous tissues after topical application of gasoline. 778 Aug 31


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