Xenobiotic Metabolite

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Ian D. Wilson - One of the best experts on this subject based on the ideXlab platform.

  • endogenous and Xenobiotic Metabolite profiling of liver extracts from scid and chimeric humanized mice following repeated oral administration of troglitazone
    Xenobiotica, 2014
    Co-Authors: Alan Barnes, David R Baker, Kirsten Hobby, Simon Ashton, Filippos Michopoulos, Konstantina Spagou, Neil Loftus, Ian D. Wilson
    Abstract:

    Abstract1. Metabonomic analysis, via a combination of untargeted and targeted liquid chromatography-mass spectrometry (LC-MS) and untargeted 1H NMR spectroscopy-based Metabolite profiling, was performed on aqueous (AQ) and organic liver extracts from control (SCID) and chimeric humanized (PXB) mice dosed with troglitazone at 0, 300 and 600 mg/kg/day for seven days.2. LC-MS analysis of AQ liver extracts showed a more “human-like” profile for troglitazone Metabolites for PXB, compared with SCID, mice.3. LC-MS detected differences in endogenous Metabolites, particularly lipid species in dosed mice, including elevated triacylglycerols and 1-alkyl,2-acylglycerophosphates as well as lowered diacylglycerophosphocholines and 1-alkyl,2-acylglycerophosphocholines for PXB compared with SCID mouse liver extracts. Following drug administration changes in the relative proportions of the ions for various unsaturated fatty acids were observed for both types of mouse, some of which were specific to PXB or SCID mice.4. 1H ...

  • Directly coupled HPLC-NMR and HPLC-NMR-MS in pharmaceutical research and development.
    Journal of Chromatography B: Biomedical Sciences and Applications, 2000
    Co-Authors: John C. Lindon, Jeremy K. Nicholson, Ian D. Wilson
    Abstract:

    Abstract The methodology for the direct coupling of HPLC with NMR spectroscopy and the simultaneous double coupling of HPLC with NMR and mass spectrometry (MS) is described. Indications of the necessary technical developments to achieve this are given, and the applications of these new techniques to studies of pharmaceutical relevance are reviewed. These include studies of combinatorial chemistry libraries, synthetic chemical impurities, characterisation of drug mixtures, identification of natural products of possible pharmaceutical interest and identification of Xenobiotic Metabolites in human, animal and in vitro systems. In addition, HPLC–NMR has been used to investigate Xenobiotic Metabolite reactivity. Finally, the potential future directions of the techniques are discussed.

Alain Minn - One of the best experts on this subject based on the ideXlab platform.

  • in vivo study of the elimination from rat brain of an intracerebrally formed Xenobiotic Metabolite 1 naphthyl β d glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, Jeanfrancois Ghersiegea, G Siest, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

  • In Vivo Study of the Elimination from Rat Brain of an Intracerebrally Formed Xenobiotic Metabolite, 1‐Naphthyl‐β‐D‐Glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, G Siest, Jean-françois Ghersi-egea, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

Brigitte Leininger - One of the best experts on this subject based on the ideXlab platform.

  • in vivo study of the elimination from rat brain of an intracerebrally formed Xenobiotic Metabolite 1 naphthyl β d glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, Jeanfrancois Ghersiegea, G Siest, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

  • In Vivo Study of the Elimination from Rat Brain of an Intracerebrally Formed Xenobiotic Metabolite, 1‐Naphthyl‐β‐D‐Glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, G Siest, Jean-françois Ghersi-egea, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

G Siest - One of the best experts on this subject based on the ideXlab platform.

  • in vivo study of the elimination from rat brain of an intracerebrally formed Xenobiotic Metabolite 1 naphthyl β d glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, Jeanfrancois Ghersiegea, G Siest, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

  • In Vivo Study of the Elimination from Rat Brain of an Intracerebrally Formed Xenobiotic Metabolite, 1‐Naphthyl‐β‐D‐Glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, G Siest, Jean-françois Ghersi-egea, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.

Jeanfrancois Ghersiegea - One of the best experts on this subject based on the ideXlab platform.

  • in vivo study of the elimination from rat brain of an intracerebrally formed Xenobiotic Metabolite 1 naphthyl β d glucuronide
    Journal of Neurochemistry, 1991
    Co-Authors: Brigitte Leininger, Jeanfrancois Ghersiegea, G Siest, Alain Minn
    Abstract:

    Abstract: Among the drug-metabolizing enzymes present in the rat brain, one form of UDP-glucuronyltransferase catalyzes the formation of the polar Metabolite 1-naphthyl-β-D-glucuronide from 1-naphthol. We measured the activity of this isoform in different brain regions and showed its heterogeneous distribution. Conjugation activities were found to be the highest in the olfactory bulbs (25.4 nmol/h/mg protein) and lowest in the cerebellum (4.5 nmol/h/mg protein). As the blood–brain barrier prevents the passage of hydrosoluble molecules, we studied in vivo the characteristics of the efflux of labeled 1-naphthyl-β-D-glucuronide injected into the lateral ventricle and the cortex tissue, using tritiated water and labeled inulin as reference compounds. The results reported here indicate that intracerebrally formed glucuronide is cleared from brain tissue by both diffusion and a saturable efflux process.