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

doi:10.1016/j.etap.2023.104343

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

Immune Endocrine and Epigenetics

Research output: Contribution to journal › Article › Research › peer-review

1 Citation (Scopus)

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 language	English
Article number	104343
Journal	Environmental Toxicology and Pharmacology
Volume	105
Early online date	19 Dec 2023
DOIs	https://doi.org/10.1016/j.etap.2023.104343
Publication status	Published - 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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Morel, C., Paoli, J., Emond, C., Debaugnies, F., Hardy, E. M., Creta, M., Montagne, M., Borde, P., Nieuwenhuyse, A. V., Duca, R. C., Schroeder, H., & Grova, N. (2024). Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane. Environmental Toxicology and Pharmacology, 105, Article 104343. https://doi.org/10.1016/j.etap.2023.104343

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

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.",

keywords = "Autism spectrum disorders (ASD), CYP450 metabolism, Foetal toxicity, Pharmacokinetic, Valproic acid model (VPA-model), α-hexabromocyclododecane (α-HBCDD)",

author = "C. Morel and J. Paoli and C. Emond and F. Debaugnies and Hardy, {E. M.} and M. Creta and M. Montagne and P. Borde and Nieuwenhuyse, {A. Van} and Duca, {R. C.} and H. Schroeder and N. Grova",

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year = "2024",

month = jan,

doi = "10.1016/j.etap.2023.104343",

language = "English",

volume = "105",

journal = "Environmental Toxicology and Pharmacology",

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Morel, C, Paoli, J, Emond, C, Debaugnies, F, Hardy, EM, Creta, M, Montagne, M, Borde, P, Nieuwenhuyse, AV, Duca, RC, Schroeder, H & Grova, N 2024, 'Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane', Environmental Toxicology and Pharmacology, vol. 105, 104343. https://doi.org/10.1016/j.etap.2023.104343

TY - JOUR

T1 - Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane

AU - Morel, C.

AU - Paoli, J.

AU - Emond, C.

AU - Debaugnies, F.

AU - Hardy, E. M.

AU - Creta, M.

AU - Montagne, M.

AU - Borde, P.

AU - Nieuwenhuyse, A. Van

AU - Duca, R. C.

AU - Schroeder, H.

AU - Grova, N.

PY - 2024/1

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N2 - 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.

AB - 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.

KW - Autism spectrum disorders (ASD)

KW - CYP450 metabolism

KW - Foetal toxicity

KW - Pharmacokinetic

KW - Valproic acid model (VPA-model)

KW - α-hexabromocyclododecane (α-HBCDD)

UR - http://www.scopus.com/inward/record.url?scp=85181925150&partnerID=8YFLogxK

UR - https://pubmed.ncbi.nlm.nih.gov/38122861

U2 - 10.1016/j.etap.2023.104343

DO - 10.1016/j.etap.2023.104343

M3 - Article

C2 - 38122861

AN - SCOPUS:85181925150

SN - 1382-6689

VL - 105

JO - Environmental Toxicology and Pharmacology

JF - Environmental Toxicology and Pharmacology

M1 - 104343

ER -

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

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Keywords

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