Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane

C. Morel, J. Paoli, C. Emond, F. Debaugnies, E. M. Hardy, M. Creta, M. Montagne, P. Borde, A. Van Nieuwenhuyse, R. C. Duca, H. Schroeder, N. Grova*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Assessing the role of α-hexabromocyclododecane α-HBCDD as a factor of susceptibility for Autism Spectrum disorders by using valproic acid-exposed rat model (VPA) required characterizing VPA pharmacokinetic in the context of α-HBCDD-co-exposure in non-pregnant and pregnant rats. The animals were exposed to α-HBCDD by gavage (100 ng/kg/day) for 12 days. This was followed by a single intraperitoneal dose of VPA (500 mg/kg) or a daily oral dose of VPA (500 mg/kg) for 3 days. Exposure to α-HBCDD did not affect the pharmacokinetics of VPA in pregnant or non-pregnant rats. Surprisingly, VPA administration altered the pharmacokinetics of α-HBCDD. VPA also triggered higher foetal toxicity and lethality with the PO than IP route. α-HBCDD did not aggravate the embryotoxicity observed with VPA, regardless of the route of exposure. Based on this evidence, a single administration of 500 mg/kg IP is the most suitable VPA model to investigate α-HBCDD co-exposure.

Original languageEnglish
Article number104343
JournalEnvironmental Toxicology and Pharmacology
Volume105
Early online date19 Dec 2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • Autism spectrum disorders (ASD)
  • CYP450 metabolism
  • Foetal toxicity
  • Pharmacokinetic
  • Valproic acid model (VPA-model)
  • α-hexabromocyclododecane (α-HBCDD)

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