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)

Microsomal cytochrome P450 content, NADPH-cytochrome c reductase, and phase I (ethoxycoumarin and ethoxyresorufin O-dealkylases) and phase II (glutathione S-transferase and UDP-glucuronyltransferase) activities were studied in the liver and intestine of the striped mullet (Mullus barbatus) for 8 months (before and during sexual maturation). Biotransformation activities were much lower in extrahepatic tissues than the corresponding activities in the liver. Intestinal and hepatic biotransformation activities presented similar seasonal fluctuations: Phase I activity increased from October to February (during water cooling) and generally decreased before spawning; Phase II activity was not greatly different. Moreover, NADPH-cytochrome c reductase, ethoxyresorufin O-dealkylase, and glutathione S-transferase activities were measured in the kidney during the sexual maturation period. Renal phase I and phase II activities showed very little fluctuation during the 5 months studied. Cytochrome P450 and ethoxycoumarin and ethoxyresorufin O-dealkylases exhibited sex-linked differences during sexual maturation, whatever the tissue: in the liver the values are higher in male fish, whereas in the intestine and kidney they are lower.
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PMID:Seasonal and sex-linked variations in hepatic and extrahepatic biotransformation activities in striped mullet (Mullus barbatus). 191 95

The effects of all-trans-retinoic acid (RA) on hepato-carcinogenesis induced by N-nitrosomorpholine (NNM) and on the expression of myc p110 proteins were investigated in male Sprague-Dawley rats. Rats received i.m. injections of RA twice a week and, from the beginning of the experiment, were given drinking water containing NNM for 8 weeks. Pre-neoplastic and neoplastic lesions staining positively for gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase placental type (GST-P) or myc p110 protein were examined histochemically. At week 18, quantitative histological analysis showed that prolonged administration of RA resulted in a significant reduction in the number, size and volume of GGT-positive and GST-P-positive hepatic lesions. Administration of RA also caused a significant increase in the proportion of myc p110-negative lesions to the total pre-neoplastic lesions observed. Myc p110-negative lesions had a significantly lower mitotic index than myc p110-positive lesions. These findings indicate that RA inhibits hepatocarcinogenesis and suggest that this effect may be related to its influence in reducing the expression of myc gene proteins and its subsequent inhibition of cell proliferation in pre-neoplastic lesions.
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PMID:Inhibition by retinoic acid of hepatocarcinogenesis induced by N-nitrosomorpholine and of expression of myc oncogene protein in Sprague-Dawley rats. 191 45

The equilibrium unfolding transition of class pi glutathione S-transferase, a homodimeric protein, from porcine lung was monitored by spectroscopic methods (fluorescence emission and ultraviolet absorption), and by enzyme activity changes. Solvent (guanidine hydrochloride and urea)-induced denaturation is well described by a two-state model involving significant populations of only the folded dimer and unfolded monomer. Neither a folded, active monomeric form nor stable unfolding intermediates were detected. The conformational stability, delta Gu (H2O), of the native dimer was estimated to be about 25.3 +/- 2 kcal/mol at 20 degrees C and pH6.5.
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PMID:Equilibrium unfolding of class pi glutathione S-transferase. 193 Feb 26

The modifying potential of allyl sulfide (AS), indole-3-carbinol (I3C) and carboxyethylgermanium sesquioxide (GE) on lesion development was examined in a wide-spectrum initiation model. Groups 1-4 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, i.p., single dose), N-methylnitrosourea (MNU) (20 mg/kg, i.p., four doses at days 2, 5, 8 and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Groups 5-7 received vehicles without carcinogens during the initiation period. Group 8 served as the untreated control. After this initiating procedure, groups 2-7 were administered a diet containing 0.5% AS or I3C and 0.05% GE. All surviving animals were killed 40 weeks after the beginning of the experiment and the target organs were examined. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with all three compounds. AS treatment significantly decreased the incidence of hepatic hyperplastic nodules, adenoma of the lung and thyroid, and papillary or nodular hyperplasia of the urinary bladder. Administration of GE also significantly inhibited the development of hepatic nodules and adenoma of the lung and thyroid. However, I3C only inhibited the hyperplastic nodules of the liver. These results demonstrated that this multi-organ initiation model could be useful in confirming organ-specific modification potential and, in addition, the inhibitory effect of AS, I3C and GE on liver, lung, thyroid and urinary bladder carcinogenesis.
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PMID:Modifying responses of allyl sulfide, indole-3-carbinol and germanium in a rat multi-organ carcinogenesis model. 201 33

For assessment of the carcinogenic potential and the mutagenicity of dipyrone, an antipyretic anodyne, -[(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl) methylamino]-methanesulfonic acid sodium salt monohydrate, three experiments were conducted using dipyrone A produced in Japan and/or dipyrone B obtained from the Federal Republic of Germany. (i) Carcinogenic potential of dipyrone A for rat liver: 8 week old male F344 rats were pretreated with 0.01% diethylnitrosamine (DEN) in drinking water for 2 weeks and, after 1 week of resting, administered 0.4% dipyrone in drinking water, 5 days a week, for 72 weeks. After an 8 week recovery period, all surviving rats were killed at 83 weeks. Hepatocellular carcinomas developed at a higher incidence in the DEN + dipyrone group (18 of 29 rats, 62%) than in the DEN alone group (9 of 29 rats, 31%), the difference being statistically significant (P less than 0.05). No carcinogenic activity of dipyrone was demonstrated in the groups given 0.4% dipyrone for 72 weeks or 0.4% dipyrone for 25 weeks, followed by 0.05% phenobarbital (PB) for 50 weeks. However, glutathione S-transferase P positive (GST-P+) preneoplastic hepatic foci in these groups were observed at a higher incidence than in the untreated control group (P less than 0.01). (ii) Effect of dipyrone A and dipyrone B on induction of DEN-initiated GST-P+ hepatic foci in a medium-term bioassay system: 0.4% dipyrone A in drinking water and 0.57% dipyrone A or dipyrone B in powdered diet after DEN initiation had similar enhancing effects on the development of GST-P+ foci (P less than 0.001). (iii) The Ames mutation test in Salmonella: both dipyrone A and dipyrone B proved weakly mutagenic for strain TA100 in the presence or absence of S9 fraction.
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PMID:Tumor promoting potential in male F344 rats and mutagenicity in Salmonella typhimurium of dipyrone. 207 Apr 86

Capsaicin (CAP; 50 mg/kg body wt., p.o.) and/or ethanol (EtOH; 10% (v/v) in the drinking water) were given for a period of 30 days to male rats, and changes in hepatic drug-metabolizing enzymes were investigated. The EtOH alone tended to increase the microsomal parameters such as cytochrome P-450 content and enzyme activities of aniline hydroxylase, aminopyrine demethylase and UDP-glucuronyl transferase, while it did not affect the cytosolic enzyme activities of sulfotransferase and glutathione S-transferase. The administration of CAP without EtOH tended to decrease all of the parameters studied. In contrast, the ingestion of CAP with EtOH tended to increase even the elevated microsomal enzyme activities by EtOH alone. These data suggest that chronic alcohol ingestion could modify the potential for detoxification of xenobiotics in persons who regularly consume a large amount of hot peppers.
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PMID:Effects of capsaicin and ethanol on hepatic drug-metabolizing enzymes in rat. 211 94

The effect of prolonged exposure to buthionine sulfoximine (BSO) on rat hepatic Phase I and Phase II drug-metabolizing enzymes has been examined. Exposure to 30 mM BSO in drinking water for 7 days induced hepatic microsomal UDP-glucuronosyltransferase activity (detergent-activated) toward p-nitrophenol (250%), 1-naphthol (210%), morphine (130%) and testosterone (140%), but not estrone. Glucuronosyltransferase activities were also induced after exposure for as short as 3 and as long as 13 days. When rats were returned to unsupplemented drinking water for 1 day prior to sacrifice following 6 days on 30 mM BSO, comparable induction to that seen after 7 consecutive days on the BSO solution was observed despite liver glutathione concentration having rebounded to 127% of control. Daily ingestion of BSO was similar (1 mmol/rat/day) for all periods of 30 mM BSO-drinking water exposure, with a body weight-adjusted dose range of 3.2-6.3 mmol/kg/day. An analogous inductive response caused by drinking 30 mM BSO for 3 days was elicited for p-nitrophenol and morphine glucuronidation by 6 mmol/kg doses of BSO given as single daily intraperitoneal or intragastric injections for 3 days. Intraperitoneal, intragastric and all BSO-drinking water exposures also significantly induced (130-195%) cytosolic glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene. Significant increases in UDP-glucuronosyltransferase and glutathione S-transferase activities were also observed following 3 days of exposure to BSO in the drinking water at a concentration as low as 5 mM. Cytosolic p-nitrophenol sulfotransferase activity, with one minor exception, was not enhanced by any BSO treatment regimen. Alterations in transferase activities were not accompanied by any major changes in either overall cytochrome P-450 concentration or oxidative reactions selective for two isozymes. Thus, in addition to its well-documented glutathione-depleting property, BSO also selectively induces several Phase II drug-metabolizing enzymes, an effect to be considered in studies employing extended BSO treatment.
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PMID:Induction of rat UDP-glucuronosyltransferase and glutathione S-transferase activities by L-buthionine-S,R-sulfoximine without induction of cytochrome P-450. 212 59

The modifying potential of Clonorchis sinensis (CS) infestation on dimethylnitrosamine (DMN)-induced hepatocarcinogenesis was studied in male F344 rats. The metacercariae of CS were infected, 60 to each animal, by a single intragastric intubation at various times, before, during or after an 8-week period of DMN (25 ppm in drinking water) treatment. Controls were treated with DMN alone or infected with CS without carcinogen. Animals killed at the end of the 40-week experimental period showed a significant enhancing effect of CS on GST-P+ foci induction when CS was infected 4 weeks before DMN treatment, although no such influence was evident with CS infection during or following DMN exposure. The present findings suggest that CS might facilitate the proliferation of DMN-induced preneoplastic lesions of liver in rats.
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PMID:Enhancement of dimethylnitrosamine-induced glutathione S-transferase P-positive hepatic foci by Clonorchis sinensis infestation in F344 rats. 219 25

The effects of ethyl alcohol and pig serum administration on the development of preneoplastic hepatic enzyme-altered foci were examined in an in vivo mid-term assay system. Rats were initially given a single dose (200 mg/Kg) intraperitoneal injection of diethylnitrosamine (DEN). Two weeks later, treatment was started with 10% ethanol + 10% sucrose solution, 10% sucrose solution, or tap water as drinking water for 6 weeks with or without intraperitoneal injection of porcine serum twice a week. All rats were subjected to a two-thirds partial hepatectomy at week 3. The modification potentials were evaluated by comparing the number and area per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the liver of each group. As a result, ethanol significantly enhanced the development of GST-P+ foci. Unfortunately, the porcine serum injection produced no hepatic fibrosis and no significant alteration in GST-P+ foci.
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PMID:The enhancing effect of ethanol on the development of glutatione S-transferase placental form-positive foci induced by diethylnitrosamine in F344 rat. 220 62

Most compounds considered to be foreign to the human body are rather hydrophobic and chemically inert. Because of their hydrophobicity, xenobiotics enter the body easily by diffusion through biological membranes, are difficult to excrete in unchanged form in the urine and bile and accumulate in hydrophobic compartments of the cell, including the phospholipid bilayer of membranes, where they can disturb normal cellular functions. In order to transform xenobiotics into products which are more readily excretable, enzymes of detoxication first activate these substances (primarily via the cytochrome P-450 monooxygenase system) to intermediates which are often highly electrophilic and reactive, such as epoxides, free radicals and carbonium ions. These intermediates are then partially inactivated and their solubility in water simultaneously increased through the addition of water (by epoxide hydrolases) or conjugation with glutathione (by glutathione transferases). Finally, an additional increase in water solubility can be achieved by conjugation with, for example, sulfate (via sulfotransferases) and/or glucuronic acid (via UDP-glucuronyltransferases). Unfortunately, reactive intermediates of xenobiotic metabolism which are not inactivated sufficiently rapidly can bind covalently to many nucleophilic groups in the cell, including those on DNA, RNA and protein. Most often, because of various cellular defense mechanisms, such binding causes no serious damage. However, in some cases toxic and/or genotoxic effects may be produced. As an alternative to experimentation with animals, we have examined xenobiotic metabolism in circulating mononuclear leukocytes from human beings. Certain enzymes of detoxication--including membrane-bound and cytosolic epoxide hydrolases and cytosolic glutathione transferases--can be easily measured and characterized in preparations from these cells. Autosomal dominant hereditary differences of at least several hundred-fold in the activity of glutathione transferase mu in circulating human lymphocytes were observed, differences which may be of value in predicting an individual's risk for toxic/genotoxic damage after exposure to certain xenobiotics.
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PMID:The metabolism of xenobiotics and its relationship to toxicity/genotoxicity: studies with human lymphocytes. 226 43


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