Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism and excretion of silybin (as N-methyl-glucamine salt) was investigated after intravenous and oral administration to rats. In the urine, silybin was excreted mostly in the unchanged form after intravenous as well as oral application, whilst in the bile it appeared above all in the form of metabolites. By hydrolysis with arylsulfatase/beta-glucuronidase, the metabolites were identified as sulfate and glucuronide conjugates of silybin and dehyrosilybin; the latter appeared in small quantities as a dehydrated product of silybin. After intravenous injection of 20 mg silybin per kg body weight, the excreted amount of silybin after 48 h was 8%, whereas 76% was eliminated in the bile within the same period of time. After oral application of 2--20 mg silybin/kg body weight 20% after 40 mg/kg 35% and after 120 mg/kg 20% of the administered silybin was excreted in the bile during 48 h. The maximum excretion rate was achieved at application of 20 mg/kg p.o. after 1 h. At this dosage, 2--5% was eliminated within the same time in the urine. The excretion of silybin mainly took place (more than 80% of the total of excreted bilybin) in the bile, both after oral and intravenous administration.
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PMID:[Studies of the metabolism and excretion of silybin in the rat]. 117 27

Twenty hair samples obtained from Bolivian mine workers who chewed 3-8 g of coca leaves daily for several years were analyzed for cocaine and its main metabolites, benzoylecgonine (BZE) and ecgonine methyl ester (EME). A new method was developed for the detection and quantitation of cocaine and its metabolites, BZE and EME, from hair in a single procedure. The hair samples were washed, cut into 56 segments (2-cm length), pulverized, and incubated with phosphate buffer and the enzyme beta-glucuronidase-arylsulfatase. After solid phase extraction and derivatization with pentafluoropropionic anhydride/pentafluoropropanol, the drugs were identified and measured by gas chromatography/mass spectrometry (GC/MS) using deuterated cocaine, BZE, and EME as internal standards. The method is reproducible (cocaine, CV = 8%; BZE, CV = 14%) and the detection limit for cocaine and BZE was 0.1 ng/mg, for EME 1 ng/mg. In the different hair segments, cocaine was found to be present in concentrations between 1.4 to 50.6 ng/mg, benzoylecgonine from 0.4 to 17.6 ng/mg, and ecgonine methyl ester traces below the calibration curve of approximately 12.9 ng/mg. In 95% of the cases cocaine exceeded BZE and EME in concentration.
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PMID:Identification and quantitation of cocaine and its metabolites, benzoylecgonine and ecgonine methyl ester, in hair of Bolivian coca chewers by gas chromatography/mass spectrometry. 129 35

We studied the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte [G]-CSF, interleukin (IL)-1, IL-3, IL-5, IL-6, and macrophage [M]-CSF) on differentiation and functional activity of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on parental HL-60 promyelocytic leukemia cells. Purified biosynthetic GM-CSF and IL-5 enhanced cell proliferation and induced eosinophilic differentiation in the eosinophilic subline in both liquid and agar cultures. IL-3 and IL-6 stimulated cell proliferation but had no effect on cell differentiation, whereas IL-1 and G-CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under the conditions tested. GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed increased O2- production in response to phorbol esters (PMA), enhanced phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta-glucuronidase and eosinophil peroxidase (EPO). The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis. G-CSF had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of Eos-HL-60 cells. IL-5 did not affect proliferation, differentiation, or enzyme release in promyelocytic HL-60 cells. These results indicate the specificity of IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on eosinophilopoiesis and mature eosinophil function in a model system, and indicate the absence of G-CSF and IL-1 stimulation of eosinophils. The Eos-HL-60 line is a useful model for studying human eosinophil responses to cytokines.
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PMID:Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors. 137 88

Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits antimutagenic activity in several short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo. The effect of CHL pretreatment on the excretion of mutagens in the urine and feces of male Sprague-Dawley rats has been studied using the Salmonella mutagenicity assay. Animals were given 1 percent CHL in the drinking water for 2 days before administering a single dose of 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) by oral gavage. Rats pretreated with CHL had higher levels of mutagens in the urine and feces compared with animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose excreted was < 4% in controls vs. 18% in rats given CHL. Mutagenicity required the presence of an activation system, was unaffected by treatment with beta-glucuronidase or arylsulfatase, and in both the urine and feces was accounted for by increased elimination of unmetabolized parent compound. The results support the view that CHL may operate in vivo as a "desmutagen" or interceptor molecule, interacting with IQ in the gut and tissues, and reducing carcinogen bioavailability.
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PMID:Chlorophyllin-enhanced excretion of urinary and fecal mutagens in rats given 2-amino-3-methylimidazo[4,5-f]quinoline. 139 10

When 2-chloro[14C]dibenzofuran was intravenously administered to the rats, about 86% of radioactivity was found in the urine, the large intestinal contents and the feces within 24 h. Approximately 3% of 2-chlorodibenzofuran (2CDF) radioactivity was present in the adipose tissue 48 h after an intravenous administration. A similar excretion pattern of the compound was observed in orally administered rats. From experiments in vitro, approximately 80% of 2CDF was present in the red blood cell fraction and the remainder in the plasma fraction. Bile cannulation studies revealed involvement of enterohepatic circulation in the metabolism of the compound. Bile specimens that were subjected to enzymatic hydrolysis by arylsulfatase and/or beta-glucuronidase showed the presence of various yet unidentified conjugated substances. A comparative study using 3-chlorodibenzofuran (3CDF) showed a similar distribution pattern in the 2CDF-treated rats, but 2CDF appeared to accumulate more in the adipose tissue and red blood cells. The present study demonstrates that most of 2CDF is quickly metabolized to give rise to a number of metabolites and excreted from the body, but suggests that the compound once distributed in the adipose tissue may remain there for a relatively long period of time.
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PMID:Disposition and excretion of 2-chlorodibenzofuran in the rat. 153 97

[3H]Benzo[a]pyrene (B[a]P) was administered to male Sprague-Dawley rats via intratracheal instillation, and bile was collected over a period of 6 h. Conjugated metabolites of B[a]P in bile were separated by paper chromatography or reversed-phase ion-pair HPLC and quantified by liquid scintillation spectrometry. In paper chromatographic analysis, a class of conjugates more polar than thioether conjugates was recognized. These conjugates were identified as quinol diglucuronides by hydrolyzing with beta-glucuronidase and analyzing products of the hydrolysis with HPLC, and by migration on paper relative to a standard of 3,6-quinol diglucuronide. From this analysis, relative amounts of conjugated metabolites of B[a]P in bile were 37.3% quinol diglucuronides, 19.9% thioether conjugates, 33.3% monoglucuronide and sulfate conjugates, and 9.4% unconjugated metabolites. Analysis by reversed-phase ion-pair HPLC provided improved resolution among the conjugates in bile. In particular, the 3,6-quinol diglucuronide was resolved from the 1,6- and 6,12-quinol diglucuronides, with identification of peaks being based on sensitivity to hydrolysis with beta-glucuronidase and elution of standards of these diglucuronides. The elution position of thioether conjugates was identified by their insensitivity to hydrolysis with beta-glucuronidase and arylsulfatase and by synthesis of thioether conjugates in V79 (XEM-2) cells, which express cytochrome P450IA1 and have relatively high levels of glutathione S-transferases but low levels of UDP-glucuronyltransferases and sulfotransferases. From the reversed-phase ion-pair HPLC analysis, relative amounts of conjugates in bile were 10.4% 1,6- and 6,12-quinol diglucuronides, 20.8% 3,6-quinol diglucuronide, 30.4% thioether conjugates, 17.8% monoglucuronides, 6.2% sulfate conjugates, and 14.4% unconjugated metabolites. These studies provide the first report of the biosynthesis of quinol diglucuronide conjugates of B[a]P in vivo and demonstrate that they are excreted into bile in significant quantities.
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PMID:Quinol diglucuronides are predominant conjugated metabolites found in bile of rats following intratracheal instillation of benzo[a]pyrene. 154 30

The metabolism of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) in rat, rabbit and dog was studied. The urine of animals dosed with 14C-KC-764 was extracted with ethyl acetate after treatment with beta-glucuronidase and arylsulfatase. The metabolites were purified by TLC and HPLC from the extract. Unchanged KC-764 and 16 metabolites were isolated and their structures were identified or proposed by NMR and MS spectrometry. The metabolism of KC-764 took place by the oxidation of the tetrahydropyridine ring, 6,7-position and 2-methyl group of the pyrazolopyridine ring, and their combinations. The oxidation of the tetrahydropyridine ring was predominant in dog, whereas the oxidation of the pyrazolopyridine ring was more important in rabbit. Rat produced the various metabolites by their combination. 6-Oxo and 6-ureido derivatives of the tetrahydropyridine ring were common major metabolites in all animal species studied.
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PMID:Identification of urinary metabolites of 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in rat, rabbit and dog. 158 80

For the enantiospecific assay of propranolol in biological material, formation of diastereomeric derivatives is one possible approach. The aim of the present study was the development and optimization of three analytical methods based on different chiral reagents: phenylethylisocyanate and the acyl chloride as well as the isocyanate that are derived from the fluorescent S-flunoxaprofen. Pronethalol is used as internal standard in all three procedures and improves the coefficients of variation significantly. After extraction from human plasma or urine, propranolol is reacted with one of these compounds in anhydrous organic solvents with addition of triethylamine. The diastereomeric derivatives are then resolved on an octadecylsilane column using mixtures of water and methanol with or without addition of glacial acetic acid. Good resolutions of the diastereomeric derivatives are found under these conditions. Conjugates are cleaved prior to analysis using beta-glucuronidase-arylsulfatase and assayed as parent propranolol enantiomers. All three procedures were suitable for analysis of propranolol enantiomers in biological samples in the lower nanogram range (1-2 ng/mL). A preliminary clinical study confirmed the known enantiospecificity in the pharmacokinetics of propranolol and showed high concentrations of conjugates with R/S ratios that were similar to those of the parent enantiomers.
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PMID:Improved enantiospecific RP-HPLC assays for propranolol in plasma and urine with pronethalol as internal standard. 168 29

For the enantiospecific assay of propranolol in biological material, formation of diastereomeric derivatives is one possible approach. The aim of the present study was the development and optimization of three analytical methods based on different chiral reagents: phenylethylisocyanate and the acyl chloride as well as the isocyanate that are derived from the fluorescent S-flunoxaprofen. Pronethalol is used as internal standard in all three procedures and improves the coefficients of variation significantly. After extraction from human plasma or urine, propanolol is reacted with one of these compounds in anhydrous organic solvents with addition of triethylamine. The diastereomeric derivatives are then resolved on an octadecylsilane column using mixtures of water and methanol with or without addition of glacial acetic acid. Good resolutions of the diastereomeric derivatives are found under these conditions. Conjugates are cleaved prior to analysis using beta-glucuronidase-arylsulfatase and assayed as parent propranolol enantiomers. All three procedures were suitable for analysis of propranolol enantiomers in biological samples in the lower nanogram range (1-2 ng/mL). A preliminary clinical study confirmed the known enantiospecificity in the pharmacokinetics of propranolol and showed high concentrations of conjugates with R/S ratios that were similar to those of the parent enantiomers.
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PMID:Improved enantiospecific RP-HPLC assays for propranolol in plasma and urine with pronethalol as internal standard. 168 58

Recent evidence confirms that cytokines such as IL-1, IL-4, IL-5, and GM-CSF may enhance or inhibit eosinophil function. Functions that are susceptible to modulation include eosinophil-mediated antibody-dependent damage of helminthic parasites, oxidative metabolism and degranulation. We have employed IgG and IgE-coated Sepharose beads to investigate selective modulation of IgG and IgE-mediated enzyme release by IL-1 beta. Both IgG and IgE-coated beads induced release of granular enzymes beta-glucuronidase and arylsulfatase. Enzyme release from IgG-stimulated eosinophils was inhibited by preincubation with IL-1 beta (100 pg/ml, P less than or equal to 0.05). In contrast, enzyme release by IgE-stimulated eosinophils was enhanced by IL-1 beta (100 pg/ml, P less than or equal to 0.05). These studies support the hypothesis that IL-1 beta has specific selective actions on eosinophil function. Furthermore, these actions on particle-stimulated enzyme release suggest that IgG and IgE mediated processes in eosinophils are differentially regulated.
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PMID:Selective regulation of eosinophil degranulation by interleukin 1 beta. 174 16


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