Consumption of watercress fails to alter coumarin metabolism in humans.
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.
Murphy
S E
SE
University of Minnesota Cancer Center, Minneapolis 55455, USA. murph062@umn.edu
Johnson
L M
LM
Losey
L M
LM
Carmella
S G
SG
Hecht
S S
SS
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001711:Biotransformation; D019607:Brassicaceae; D003374:Coumarins / Q000493:pharmacokinetics*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D012016:Reference Values
D003374:Coumarins; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6