Comparative embryotoxicity of different antimalarial peroxides: In vitro study using the rat whole embryo culture model (WEC)

Monica Longo, Sara Zanoncelli, Marco Brughera, Paolo Colombo, Sergio Wittlin, Jonathan L. Vennerstrom, Joerg Moehrle, J. Carl Craft

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Three groups of compounds: (i) active peroxides (artemisinin and arterolene), (ii) inactive non-peroxidic derivatives (deoxyartemisinin and carbaOZ277) and (iii) inactive peroxide (OZ381) were tested by WEC system to provide insights into the relationship between chemical structure and embryotoxic potential, and to assess the relationship between embryotoxicity and antimalarial activity.Deoxyartemisinin, OZ381 and carbaOZ277 did not affect rat embryonic development. Artemisinin and arterolane affected primarily nucleated red blood cells (RBCs), inducing anemia and subsequent tissue damage in rat embryos, with NOELs for RBC damage at 0.1 and 0.175μg/mL, respectively. These data support the idea that only active antimalarial peroxides are able to interfere with normal embryonic development. In an attempt to establish whether and to what extent activity as antimalarials and embryotoxicity can be divorced, IC50s for activity in Plasmodium falciparum strains and the NOELs for RBCs were compared. From this comparison, arterolane showed a better safety margin than artemisinin.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalReproductive Toxicology
Volume30
Issue number4
DOIs
StatePublished - Dec 2010

Keywords

  • Artemisinins
  • Embryotoxicity
  • Malaria
  • Plasmodium falciparum
  • Primitive red blood cells
  • Synthetic peroxides
  • Whole embryo culture

ASJC Scopus subject areas

  • Toxicology

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