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

Environ Toxicol Pharmacol

Calbinotox EA-7488, Faculty of Science and Technology, University of Lorraine, Campus Aiguillettes, B.P. 70239, 54506 Vandœuvre-lès-Nancy, France; UMR Inserm 1256 nGERE, Nutrition-Génétique et exposition aux risques environnementaux, Institute of Medical Research (Pôle BMS) - University of Lorraine, B.P. 184, 54511 Nancy, France; Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity-Luxembourg Institute of Health, 29 rue Henri Koch, L-4354, Esch-Sur-Alzette, Grand Duchy of Luxembourg. Electronic address:

Published: January 2024

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2023.104343DOI Listing

Publication Analysis

Top Keywords

vpa
9
autism spectrum
8
rat model
8
dose vpa
8
vpa 500 mg/kg
8
α-hbcdd
6
pharmacokinetic characterisation
4
characterisation valproate
4
valproate autism
4
spectrum disorder
4

Similar Publications

Objective: This study aimed to establish an optimal model based on machine learning (ML) to predict Valproic acid (VPA) trough concentrations in Chinese adult epilepsy patients.

Methods: A single-center retrospective study was carried out at the Jinshan Hospital affiliated with Fudan University from January 2022 to December 2023. A total of 102 VPA trough concentrations were split into a derivation cohort and a validation cohort at a ratio of 8:2.

View Article and Find Full Text PDF

Objective: An increasing number of antiseizure medications (ASMs) are approved for monotherapy for focal epilepsy, but direct comparisons of the lifetime cost-effectiveness of all existing treatment strategies are lacking. This study aims to compare the cost-effectiveness of new ASMs and traditional ASMs as first-line monotherapy for newly diagnosed focal epilepsy.

Method: We used a Markov model to evaluate the lifetime cost-effectiveness of 10 ASMs in the treatment of focal epilepsy, with lacosamide (LCM) as a control, from the perspective of society in the United States.

View Article and Find Full Text PDF

Vagus nerve stimulation rescues impaired fear extinction and social interaction in a rat model of autism spectrum disorder.

J Affect Disord

January 2025

Department of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, 800 W Campbell Rd., Richardson, TX 75080, USA; Texas Biomedical Device Center (TxBDC), The University of Texas at Dallas, 800 W Campbell Rd., Richardson, TX 75080, USA. Electronic address:

Clinical diagnosis of anxiety disorders is highly prevalent in autism spectrum disorders (ASD). Available treatments for anxiety offer limited efficacy in the ASD population. Vagus nerve stimulation (VNS) has an anxiolytic effect in rats and, when coupled with fear extinction training, VNS enhances extinction of fear in healthy rats.

View Article and Find Full Text PDF

Soil microbial communities play a vital role in accelerating nutrient cycling and stabilizing ecosystem functions in forests. However, the diversity of soil microbiome and the mechanisms driving their distribution patterns along elevational gradients in montane areas remain largely unknown. In this study, we investigated the soil microbial diversity along an elevational gradient from 650 m to 3,800 m above sea level in southeast Tibet, China, through DNA metabarcode sequencing of both the bacterial and fungal communities.

View Article and Find Full Text PDF

Autism spectrum disorder (ASD) is marked by neurobehavioral developmental deficits, potentially linked to disrupted neuron-glia interactions. The astroglia Kir4.1 channel plays a vital role in regulating potassium levels during neuronal activation, and mutations in this channel have been associated with ASD.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!