Journal Article

Effects of dietary broccoli on human <i>in vivo</i> drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism

Morten A. Kall, Ole Vang and JØrgen Clausen

in Carcinogenesis

Volume 17, issue 4, pages 793-799
Published in print April 1996 | ISSN: 0143-3334
Published online April 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.4.793
Effects of dietary broccoli on human in vivo drug
                    metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone
                    metabolism

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Ingestion of cruciferous vegetables may prevent chemically induced carcinogenesis by their influence on specific cytochrome P450 enzymes (CYP) and phase II drug metabolizing enzymes in humans and rodents. Thus CYP enzymes are involved in transformation of procarcinogens, mutagens, steroid hormones and a large variety of other endogenous and exogenous components. In order to learn more about the influence of cruciferous vegetables on drug metabolizing enzymes in man two CYP enzymespreviously suggested to be induced by vegetables were selected in an in vivo experiment in humans. Sixteen healthy non-smoking subjects, two females and 14 males, were exposed to three different types of diets and afterwards assayed for CYP1A2 catalysed caffeine metabolites and for CYP2E1 catalysed 6-hydroxylation of chlorzoxazone. Further, 2-hydroxyoestrone: 16α-hydroxyoestrone ratios were determined in urine by means of a monoclonal antibody-based enzyme immuno assay. The three dietary periods were: (A) a customary home diet; (B) a 6 day standard diet avoiding well-known dietary inducers and inhibitors of CYP; (C) a 12 day dietary supplement to the standard diet of 500 g/day broccoli. The average 6-hydroxychlorzoxazone: chlorzoxazone ratio decreased by 21% (P < 0.05) after diet B compared with diet A in a 2 h plasma sample after ingestion of 500 mg chlorzoxazone. The ratio increased by 19% after diet C, however, this was not statistically significant. The caffeine metabolic ratio (CMR) was determined in urine 6 h after ingestionof 100 mg caffeine. The mean CMR increased by 5.5% when changing from diet A to diet B. When shifting to diet C themean CMR increased a further 19% (P< 0.0005). The average 2-hydroxyoestrone: 16α-hydroxyoestrone ratio decreased by 1.3% when comparing diet A with diet B. Daily broccoli intake increased the ratio by 29.5% (P< 0.05). A low correlation of CMR with the 2-hydroxyoestrone: 16α-hydroxyoestrone ratio indicates that humanCYP1A2 and other CYP enzymes involved in oestrone 2-hydroxylation are induced by dietary broccoli. On the other hand, the catalytic activity of CYP2E1 is not affected to the same degree by dietary broccoli.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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