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Rapid CommunicationShort Communication

Consumption of Watercress Fails to Alter Coumarin Metabolism in Humans

Sharon E. Murphy, Lisa M. Johnson, London M. Losey, Steven G. Carmella and Stephen S. Hecht
Drug Metabolism and Disposition June 2001, 29 (6) 786-788;
Sharon E. Murphy
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Lisa M. Johnson
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London M. Losey
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Steven G. Carmella
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Stephen S. Hecht
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Abstract

Watercress is an excellent source of phenethyl isothiocyanate (PEITC), an effective inhibitor of nitrosamine carcinogenesis in rodents. The mechanism of inhibition is believed to be due in part to inhibition of cytochrome P450 (P450) enzymes. P450 2A6 is a catalyst for the metabolic activation of several nitrosamines. In this study, we investigated the effect of watercress consumption on coumarin 7-hydroxylation, a P450 2A6-specific reaction, in a group of 15 nonsmoking, healthy volunteers. The urinary excretion of 7-hydroxycoumarin (7OHC) was determined. For 6 of the 15 subjects, watercress consumption decreased the amount of 7OHC excreted in the first 2 h following coumarin administration. However, the mean 0- to 2-h excretion of 7OHC for all 15 subjects was not significantly lowered by the consumption of watercress, 2.8 ± 0.78 versus 3.1 ± 0.53 mg (±S.D.). The mean 7OHC excreted from 2 to 4 h (1.1 ± 0.50 mg) was significantly higher (P = 0.027) during watercress consumption than before (0.77 ± 0.22 mg), suggesting a delay in coumarin metabolism. Total excretion of 7OHC was unaffected by watercress consumption. Therefore, under the conditions of our study, PEITC and other constituents of watercress had at most a marginal inhibitory effect on P450 2A6-catalyzed coumarin 7-hydroxylation.

Footnotes

  • Send reprint requests to: Dr. Sharon E. Murphy, University of Minnesota Cancer Center, Box 806 Mayo, 420 Delaware St. SE, Minneapolis, MN 55455. E-mail: murph062{at}umn.edu

  • This study was supported by Grant CA-46535 from the National Cancer Institute and a grant from the University of Minnesota Cancer Center.

  • Abbreviations used are::
    PEITC
    phenethyl isothiocyanate
    PEITC-NAC
    N-acetyl-S-(N-phenethylthiocarbamoyl)-l-cysteine
    NBzMA
    N-nitrosobenzylmethylamine
    NNAL
    4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
    NNAL-Gluc
    [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]β-O-d-glucosiduronic acid
    NNK
    4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
    7OHC
    7-hydroxycoumarin
    P450
    cytochrome P450
    • Received April 4, 2000.
    • Accepted February 7, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 29 (6)
Drug Metabolism and Disposition
Vol. 29, Issue 6
1 Jun 2001
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Rapid CommunicationShort Communication

Consumption of Watercress Fails to Alter Coumarin Metabolism in Humans

Sharon E. Murphy, Lisa M. Johnson, London M. Losey, Steven G. Carmella and Stephen S. Hecht
Drug Metabolism and Disposition June 1, 2001, 29 (6) 786-788;

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Rapid CommunicationShort Communication

Consumption of Watercress Fails to Alter Coumarin Metabolism in Humans

Sharon E. Murphy, Lisa M. Johnson, London M. Losey, Steven G. Carmella and Stephen S. Hecht
Drug Metabolism and Disposition June 1, 2001, 29 (6) 786-788;
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