Human metabolites of brevetoxin PbTx-2: Identification and confirmation of structure

Toxicon. 2010 Sep 15;56(4):648-51. doi: 10.1016/j.toxicon.2010.06.007. Epub 2010 Jun 17.

Abstract

Four metabolites were identified upon incubation of brevetoxin (PbTx-2) with human liver microsomes. Chemical transformation of PbTx-2 confirmed the structures of three known metabolites BTX-B5, PbTx-9 and 41, 43-dihydro-BTX-B5 and a previously unknown metabolite, 41, 43-dihydro-PbTx-2. These metabolites were also observed upon incubation of PbTx-2 with nine human recombinant cytochrome P450s (1A1, 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5). Cytochrome P450 3A4 produced oxidized metabolites while other CYPs generated the reduced products.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism
  • Humans
  • Marine Toxins / chemistry
  • Marine Toxins / metabolism*
  • Microsomes, Liver / metabolism
  • Oxocins
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Marine Toxins
  • Oxocins
  • Ptychodiscus brevis T2 toxin
  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System