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Dietary indole-3-carbinol inhibits FMO activity and the expression of flavin-containing monooxygenase form 1 in rat liver and intestine.
Drug Metab Dispos. 1996 Sep; 24(9):927-31.DM

Abstract

Indole-3-carbinol (I3C), a naturally occurring component of cruciferous vegetables, has been shown to be an effective cancer chemopreventative agent in a number of animal models, and is currently being evaluated in human clinical trials. One proposed mechanism of action for I3C involves binding of I3C acid condensation products (formed in the stomach) to the Ah receptor, with resultant induction of both Phase I and Phase II enzymes. We have previously shown that dietary administration of I3C to male Fischer 344 rats markedly induces hepatic levels of CYP1A1, and to a lesser degree CYP1A2, CYP2B1/2, and CYP3A1/2. We now report that such treatment concurrently inhibits both the activity and expression of flavin-containing monooxygenase (FMO) form 1 in rat liver and intestine. This inhibition demonstrates both a time and dose dependency, resulting in an 8-fold reduction in expression of FMO1 in liver, and almost total ablation of FMO1 in intestinal tissues at the highest dietary I3C levels examined. There are many examples of xenobiotics that are metabolized by both the CYP and FMO monooxygenase systems. In many cases these enzyme systems produce different metabolites, which often have strikingly disparate toxicological and/or therapeutic properties. Therefore, the marked shift in the ratio of FMO/CYP levels in the livers (and other tissues) of rats fed I3C may result in significant alterations in the metabolism, disposition, and toxicity of xenobiotics. Testing for a similar phenomenon in humans would seem advisable before wide-spread administration.

Authors+Show Affiliations

Toxicology Program, Oregon State University, Corvallis 97331-6602, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8886600

Citation

Larsen-Su, S, and D E. Williams. "Dietary Indole-3-carbinol Inhibits FMO Activity and the Expression of Flavin-containing Monooxygenase Form 1 in Rat Liver and Intestine." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 24, no. 9, 1996, pp. 927-31.
Larsen-Su S, Williams DE. Dietary indole-3-carbinol inhibits FMO activity and the expression of flavin-containing monooxygenase form 1 in rat liver and intestine. Drug Metab Dispos. 1996;24(9):927-31.
Larsen-Su, S., & Williams, D. E. (1996). Dietary indole-3-carbinol inhibits FMO activity and the expression of flavin-containing monooxygenase form 1 in rat liver and intestine. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 24(9), 927-31.
Larsen-Su S, Williams DE. Dietary Indole-3-carbinol Inhibits FMO Activity and the Expression of Flavin-containing Monooxygenase Form 1 in Rat Liver and Intestine. Drug Metab Dispos. 1996;24(9):927-31. PubMed PMID: 8886600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary indole-3-carbinol inhibits FMO activity and the expression of flavin-containing monooxygenase form 1 in rat liver and intestine. AU - Larsen-Su,S, AU - Williams,D E, PY - 1996/9/1/pubmed PY - 1996/9/1/medline PY - 1996/9/1/entrez SP - 927 EP - 31 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 24 IS - 9 N2 - Indole-3-carbinol (I3C), a naturally occurring component of cruciferous vegetables, has been shown to be an effective cancer chemopreventative agent in a number of animal models, and is currently being evaluated in human clinical trials. One proposed mechanism of action for I3C involves binding of I3C acid condensation products (formed in the stomach) to the Ah receptor, with resultant induction of both Phase I and Phase II enzymes. We have previously shown that dietary administration of I3C to male Fischer 344 rats markedly induces hepatic levels of CYP1A1, and to a lesser degree CYP1A2, CYP2B1/2, and CYP3A1/2. We now report that such treatment concurrently inhibits both the activity and expression of flavin-containing monooxygenase (FMO) form 1 in rat liver and intestine. This inhibition demonstrates both a time and dose dependency, resulting in an 8-fold reduction in expression of FMO1 in liver, and almost total ablation of FMO1 in intestinal tissues at the highest dietary I3C levels examined. There are many examples of xenobiotics that are metabolized by both the CYP and FMO monooxygenase systems. In many cases these enzyme systems produce different metabolites, which often have strikingly disparate toxicological and/or therapeutic properties. Therefore, the marked shift in the ratio of FMO/CYP levels in the livers (and other tissues) of rats fed I3C may result in significant alterations in the metabolism, disposition, and toxicity of xenobiotics. Testing for a similar phenomenon in humans would seem advisable before wide-spread administration. SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/8886600/Dietary_indole_3_carbinol_inhibits_FMO_activity_and_the_expression_of_flavin_containing_monooxygenase_form_1_in_rat_liver_and_intestine_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8886600 DB - PRIME DP - Unbound Medicine ER -