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In vitro hepatic biotransformation of the algal toxin pectenotoxin-2

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,...

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Autores principales: Sandvik, Morten, Miles, Christopher O., Wilkins, Alistair L., Fæste, Christiane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285913/
https://www.ncbi.nlm.nih.gov/pubmed/32550586
http://dx.doi.org/10.1016/j.toxcx.2020.100031
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author Sandvik, Morten
Miles, Christopher O.
Wilkins, Alistair L.
Fæste, Christiane
author_facet Sandvik, Morten
Miles, Christopher O.
Wilkins, Alistair L.
Fæste, Christiane
author_sort Sandvik, Morten
collection PubMed
description 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.
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spelling pubmed-72859132020-06-16 In vitro hepatic biotransformation of the algal toxin pectenotoxin-2 Sandvik, Morten Miles, Christopher O. Wilkins, Alistair L. Fæste, Christiane Toxicon X Paper 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. Elsevier 2020-03-23 /pmc/articles/PMC7285913/ /pubmed/32550586 http://dx.doi.org/10.1016/j.toxcx.2020.100031 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Paper
Sandvik, Morten
Miles, Christopher O.
Wilkins, Alistair L.
Fæste, Christiane
In vitro hepatic biotransformation of the algal toxin pectenotoxin-2
title In vitro hepatic biotransformation of the algal toxin pectenotoxin-2
title_full In vitro hepatic biotransformation of the algal toxin pectenotoxin-2
title_fullStr In vitro hepatic biotransformation of the algal toxin pectenotoxin-2
title_full_unstemmed In vitro hepatic biotransformation of the algal toxin pectenotoxin-2
title_short In vitro hepatic biotransformation of the algal toxin pectenotoxin-2
title_sort in vitro hepatic biotransformation of the algal toxin pectenotoxin-2
topic Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285913/
https://www.ncbi.nlm.nih.gov/pubmed/32550586
http://dx.doi.org/10.1016/j.toxcx.2020.100031
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