Para-nitrophenol glucuronidation and sulfation in rat and human liver slices

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Summary

Para-nitrophenol (PNP) is a well-known substrate for both phase I (hydroxylation at cytochrome P450) and phase II reactions (glucuronidation and sulfation). HPLC separation of PNP conjugates has already been described, but not for respective studies with liver slices, which nowadays have proven to be a suitable model for metabolic studies. Therefore we adapted an HPLC method for the simultaneous measurement of PNP glucuronidation (PNP-G) and sulfation (PNP-S) in this in vitro system. Both activities are substantially maintained over an incubation period of 24 h. PNP-G activity, however, seems to be better preserved, as indicated by stable values for PNP-G but reduced PNP-S values after 48 h liver slice preincubation. 24 h exposure of the slices to beta-naphthoflavone or phenobarbital does not change PNP-G or PNP-S activities.

References (53)

  • G.J. Dutton et al.

    Assays for UDPglucuronyltransferase activities

    Methods Enzymol

    (1981)
  • R. Glöckner et al.

    Ethoxycoumarin O-deethylation (ECOD) activity in rat liver slices exposed to beta-naphthoflavone (BNF) in vitro

    Exp Toxic Pathol

    (1995)
  • A. Kern et al.

    Drug metabolism in hepatocyte sandwich cultures of rats and humans

    Biochem Pharmacol

    (1997)
  • U.D. Kuhn et al.

    Induction of cytochrome P450 1A1 in rat liver slices by 7-ethoxycoumarin and 4-methyl-7-ethoxycoumarin

    Exp Toxic Pathol

    (1998)
  • W. Lilienblum et al.

    Differential induction of rat liver microsomal UDP-glucuronosyltransferase activities by various inducing agents

    Biochem Pharmacol

    (1982)
  • J.H. Meerman et al.

    Sex differences in sulfation and glucuronidation of phenol, 4-nitrophenol and N-hydroxy-2-acetylaminofluorene in the rat in vivo

    Biochem Pharmacol

    (1987)
  • M.E. Morris et al.

    High-performance liquid chromatographic analysis of p-nitrophenol and its conjugates in biological samples

    J Chromatogr

    (1990)
  • D. Müller et al.

    Monooxygenation, cytochrome P4501A1 and P4501A1-mRNA in rat liver slices exposed to beta-naphthoflavone and dexamethasone in vitro

    Exp Toxic Pathol

    (1996)
  • D. Müller et al.

    Monooxygenation, cytochrome P450-mRNA expression and other functions in precision-cut rat liver slices

    Exp Toxic Pathol

    (1998)
  • D. Müller et al.

    Induction of cytochrome P450 2B1-mRNA and pentoxyresorufin O-depentylation after exposure of precision-cut liver slices to phenobarbital

    Toxicology

    (2000)
  • A. Plewka et al.

    The influence of age and some inducers on UDP-glucuronyltransferase activity

    Exp Gerontol

    (1997)
  • R.B. Raftogianis et al.

    Human phenol sulfotransferases SULT1A2 and SULT1A1: genetic polymorphisms, allozyme properties, and humanliver genotype-phenotype correlations

    Biochem Pharmacol

    (1999)
  • S.T. Saarikoski et al.

    Induction of UDP-glycosyltransferase family 1 genes in rat liver: Different patterns of mRNA expression with two inducers, 3-methylcholanthrene and beta-naphthoflavone

    Biochem Pharmacol

    (1998)
  • R.D. Sekura et al.

    Aryl sulfotransferases

    Methods Enzymol

    (1981)
  • W. Tassaneeyakul et al.

    High-performance liquid chromatographic assay for 4-nitrophenol hydroxylation, a putative cytochrome P-4502E1 activity, in human liver microsomes

    J Chromatogr

    (1993)
  • M.J. Thompson et al.

    High-performance liquid chromatographic determination of phenol, 4-nitrophenol, beta-naphthol and a number of their glucuronide and sulphate conjugates in organ perfusate

    J Chromatogr B: Biomed Appl

    (1996)
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