In vitro and in vivo inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles

The effect of consumption of glucosinolate-containing Brussels sprouts on f lavin-containing monooxygenase functional activity in humans was investigat ed in 10 healthy, male, non-smoking volunteers. After a S-week run-in perio d, 5 volunteers continued on a glucosinolate-free diet for 3 weeks (control group), and 5 others consumed 300 g of cooked Brussels sprouts per day (sp routs group). Human flavin-containing monooxygenase activity was measured b y determining the levels of urinary trimethylamine and trimethylamine N-oxi de. In the control group similar trimethylamine to trimethylamine N-oxide r atios were observed, while in the sprouts group the trimethylamine to trime thylamine N-oxide ratios were increased 2.6- to 3.2-fold, and thus flavin-c ontaining monooxygenase functional activity was decreased significantly. To investigate the molecular basis for the in vivo inhibition of functional h uman flavin-containing monooxygenase activity, in vitro studies were carrie d out examining the effect of acid condensation products of indole-3-carbin ol, anticipated to be formed after transit of Brussels sprouts through the gastrointestinal system, on the prominent cDNA-expressed human flavin-conta ining monooxygenase form 3 enzymes. Two indole-containing materials were ob served to be potent inhibitors of human flavin-containing monooxygenases, h aving K-i, values in the low micromolar range. The results suggested that a cid condensation products expected to be formed upon transit of Brussels sp routs materials through the gastrointestinal system were potent competitive inhibitors of human flavin-containing monooxygenase form 3 enzymes. The fi ndings indicate that daily intake of Brussels sprouts may lead to a decreas e in human flavin-containing monooxygenase activity, and this may have cons equences for metabolism of other xenobiotics or dietary constituents. (C) 1 999 Elsevier Science Inc.