European Journal of Drug Metabolism and Pharmacokinetics

, Volume 26, Issue 4, pp 235-240

First online:

Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate

  • Erden BanogluAffiliated withDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University
  • , Gautam G. JhaAffiliated withBiomedical Sciences, University of Rhode Island
  • , Roberta S. KingAffiliated withBiomedical Sciences, University of Rhode Island

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


The aim of our study was to determine which microsomal cytochrome P450 isozyme(s) were responsible for the microsomal oxidation of indole to indoxyl, an important intermediate in the information of the uremic toxin indoxyl sulfate. Indole was incubated together with an NADPH — generating system and rat liver microsomes. Formation of indigo, an auto-oxidation product of indoxyl, was used to determine the indole-3-hydroxylation activity. Apparent Km and Vmax values of 0.85 mM and 1152 pmol min−1 mg−1 were calculated for the formation of indoxyl from indole using rat liver microsomes. The effects of various potential inducers and inhibitors on the metabolism of indole to indoxyl by rat liver microsomes were studied to elucidate the enzymes responsible for metabolism. Studies with general and isozyme-specific P450 inhibitors demostrated that P450 enzymes and not FMO are responsible for the formation of indoxyl. In the induction studies, rate of indoxyl formation in the microsomes from untreated vs induced rats correlated nearly exactly with the CYP2E1 activity (4-nitrophenol 2-hydroxylation). These results suggests that CYP2E1 is the major isoform for the microsomal oxidation of indole to indoxyl.


Indole indoxyl cytochrome P450 oxidation metabolism