A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission

Toxicology and Applied Pharmacology
Karine AudouzePhilippe Grandjean

Abstract

The need to prevent developmental brain disorders has led to an increased interest in efficient neurotoxicity testing. When an epidemic of microcephaly occurred in Brazil, Zika virus infection was soon identified as the likely culprit. However, the pathogenesis appeared to be complex, and a larvicide used to control mosquitoes responsible for transmission of the virus was soon suggested as an important causative factor. Yet, it is challenging to identify relevant and efficient tests that are also in line with ethical research defined by the 3Rs rule (Replacement, Reduction and Refinement). Especially in an acute situation like the microcephaly epidemic, where little toxicity documentation is available, new and innovative alternative methods, whether in vitro or in silico, must be considered. We have developed a network-based model using an integrative systems biology approach to explore the potential developmental neurotoxicity, and we applied this method to examine the larvicide pyriproxyfen widely used in the prevention of Zika virus transmission. Our computational model covered a wide range of possible pathways providing mechanistic hypotheses between pyriproxyfen and neurological disorders via protein complexes, thus adding...Continue Reading

Citations

Oct 10, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Marylène RugardKarine Audouze
Jun 13, 2020·Critical Reviews in Toxicology·Deepika DeepikaVikas Kumar
Jan 23, 2021·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Adriana Raquel de Almeida da AnunciaçãoMaria Angelica Miglino

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