In vitro hepatic biotransformation of the algal toxin pectenotoxin-2

Morten Sandvik; Christopher O Miles; Alistair L Wilkins; Christiane Fæste

doi:10.1016/j.toxcx.2020.100031

In vitro hepatic biotransformation of the algal toxin pectenotoxin-2

Toxicon X. 2020 Mar 23:6:100031. doi: 10.1016/j.toxcx.2020.100031. eCollection 2020 Jun.

Authors

Morten Sandvik¹, Christopher O Miles^{1

2}, Alistair L Wilkins^{1

3}, Christiane Fæste¹

Affiliations

¹ Norwegian Veterinary Institute, P. O. Box 750 Sentrum, NO-0106, Oslo, Norway.
² Biotoxin Metrology, Measurement Science and Standards, National Research Council, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada.
³ Waikato University, Private Bag 3105, Hamilton, 3240, New Zealand.

Abstract

We have investigated the in vitro metabolism of pectenotoxin-2 (PTX-2) using primary hepatocytes from Wistar rats in suspension. Purified PTX-2 was rapidly metabolized. Two major and several minor oxidized PTX-2 metabolites were formed, none of which had retention times corresponding to PTX-1, -11, or -13. Hydrolysis products, such as PTX-2 seco acid, were not observed. Preliminary multi-stage LC-MS analyses indicated that the major hepatic PTX-2 metabolites resulted from the insertion of an oxygen atom at the positions C-19 to C-24, or at C-44. The rapid oxidative metabolism may explain the low oral toxicity of PTXs observed in vivo studies.