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

Karine Audouze, Olivier Taboureau, Philippe Grandjean

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Resumé

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 to the plausibility of pyriproxyfen neurotoxicity. Although providing only tentative evidence and comparisons with retinoic acid, our computational systems biology approach is rapid and inexpensive. The case study of pyriproxyfen illustrates its usefulness as an initial or screening step in the assessment of toxicity potentials of chemicals with incompletely known toxic properties.

OriginalsprogEngelsk
TidsskriftToxicology and Applied Pharmacology
Vol/bind354
Sider (fra-til)56-63
ISSN0041-008X
DOI
StatusUdgivet - sep. 2018

Fingeraftryk

pyriproxyfen
Systems Biology
Viruses
Microcephaly
Toxicity
Mosquito control
Mosquito Control
Poisons
Tretinoin
Nervous System Diseases
Computational Biology
Documentation
Computer Simulation
Brain
Screening
Zika Virus
Testing
Research

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title = "A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission",
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 to the plausibility of pyriproxyfen neurotoxicity. Although providing only tentative evidence and comparisons with retinoic acid, our computational systems biology approach is rapid and inexpensive. The case study of pyriproxyfen illustrates its usefulness as an initial or screening step in the assessment of toxicity potentials of chemicals with incompletely known toxic properties.",
keywords = "Journal Article, Pesticide, Predictive toxicology, Systems biology, Toxicity testing, Pyriproxyfen, Developmental neurotoxicity, Computational biology, Microcephaly/chemically induced, Insecticides/adverse effects, Zika Virus/pathogenicity, Humans, Mosquito Control/methods, Larva/drug effects, Culicidae/drug effects, Insect Vectors, Risk Assessment, Neurotoxicity Syndromes/etiology, Signal Transduction/drug effects, Protein Interaction Maps/drug effects, Pyridines/adverse effects, Animals, Zika Virus Infection/prevention & control, Toxicity Tests, Systems Biology/methods",
author = "Karine Audouze and Olivier Taboureau and Philippe Grandjean",
note = "Copyright {\circledC} 2018. Published by Elsevier Inc.",
year = "2018",
month = "9",
doi = "10.1016/j.taap.2018.02.014",
language = "English",
volume = "354",
pages = "56--63",
journal = "Toxicology and Applied Pharmacology",
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publisher = "Heinemann",

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A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission. / Audouze, Karine; Taboureau, Olivier; Grandjean, Philippe.

I: Toxicology and Applied Pharmacology, Bind 354, 09.2018, s. 56-63.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission

AU - Audouze, Karine

AU - Taboureau, Olivier

AU - Grandjean, Philippe

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2018/9

Y1 - 2018/9

N2 - 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 to the plausibility of pyriproxyfen neurotoxicity. Although providing only tentative evidence and comparisons with retinoic acid, our computational systems biology approach is rapid and inexpensive. The case study of pyriproxyfen illustrates its usefulness as an initial or screening step in the assessment of toxicity potentials of chemicals with incompletely known toxic properties.

AB - 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 to the plausibility of pyriproxyfen neurotoxicity. Although providing only tentative evidence and comparisons with retinoic acid, our computational systems biology approach is rapid and inexpensive. The case study of pyriproxyfen illustrates its usefulness as an initial or screening step in the assessment of toxicity potentials of chemicals with incompletely known toxic properties.

KW - Journal Article

KW - Pesticide

KW - Predictive toxicology

KW - Systems biology

KW - Toxicity testing

KW - Pyriproxyfen

KW - Developmental neurotoxicity

KW - Computational biology

KW - Microcephaly/chemically induced

KW - Insecticides/adverse effects

KW - Zika Virus/pathogenicity

KW - Humans

KW - Mosquito Control/methods

KW - Larva/drug effects

KW - Culicidae/drug effects

KW - Insect Vectors

KW - Risk Assessment

KW - Neurotoxicity Syndromes/etiology

KW - Signal Transduction/drug effects

KW - Protein Interaction Maps/drug effects

KW - Pyridines/adverse effects

KW - Animals

KW - Zika Virus Infection/prevention & control

KW - Toxicity Tests

KW - Systems Biology/methods

U2 - 10.1016/j.taap.2018.02.014

DO - 10.1016/j.taap.2018.02.014

M3 - Journal article

VL - 354

SP - 56

EP - 63

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

ER -