Structure Elucidation of Acid Reaction Products of indole-3-carbinol: Detection in Vivo and Enzyme Induction in Vitro

Chem Biol Interact. 1991;80(3):303-15. doi: 10.1016/0009-2797(91)90090-t.

Abstract

The potency of indole-3-carbinol (I3C) to form condensation products under acidic aqueous conditions was studied. After identifying a known dimer, 3,3'-diindolylmethane (DIM), we elucidated the structures of two trimers also found in acid reaction mixtures: 5,6,11,12,17,18-hexahydrocyclonona[1,2-b:4,5-b':7,8-b"]tri-indole (CTI), and 2,3-bis[3-indolylmethyl] indole (BII). The formation of these indole oligomers was shown to be pH dependent. The highest amounts of DIM and BII were formed in aqueous solutions having a pH value ranging from 4 to 5. No CTI could be detected at pH values above 4.5. In rats that received an oral dose of I3C we could detect DIM and BII in gastric contents, stomach tissue, small intestine and liver. No CTI could be detected in vivo after oral exposure to I3C. In in vitro experiments, using rat hepatocytes, the cytochrome P-450IA1 apoprotein level, 7-ethoxyresorufin O-deethylation activity (EROD) and DT-diaphorase activity (DTD) were markedly enhanced by DIM and CTI as well as BII.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Enzyme Induction / drug effects
  • Hydrogen-Ion Concentration
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Indoles / pharmacology
  • Liver / drug effects
  • Magnetic Resonance Spectroscopy
  • Male
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis
  • Oxidoreductases / biosynthesis
  • Rats
  • Rats, Inbred Strains

Substances

  • Indoles
  • Cytochrome P-450 Enzyme System
  • indole-3-carbinol
  • Oxidoreductases
  • Cytochrome P-450 CYP1A1
  • NAD(P)H Dehydrogenase (Quinone)
  • 3,3'-diindolylmethane