A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission
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| Titel: | A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission |
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| Autoren: | Karine Audouze, Olivier Taboureau, Philippe Grandjean |
| Quelle: | Audouze, K, Taboureau, O & Grandjean, P 2018, ' A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission ', Toxicology and Applied Pharmacology, vol. 354, pp. 56-63 . https://doi.org/10.1016/j.taap.2018.02.014 |
| Verlagsinformationen: | Elsevier BV, 2018. |
| Publikationsjahr: | 2018 |
| Schlagwörter: | 0301 basic medicine, Insecticides, Zika Virus Infection/prevention & control, Mosquito Control, Systems Biology/methods, Pyridines, Zika Virus/pathogenicity, Risk Assessment, Computational biology, Mosquito Control/methods, Larva/drug effects, 03 medical and health sciences, Predictive toxicology, Signal Transduction/drug effects, Toxicity Tests, Journal Article, Microcephaly/chemically induced, Animals, Humans, Protein Interaction Maps, Insecticides/adverse effects, Pyridines/adverse effects, 0303 health sciences, Zika Virus Infection, Systems Biology, Neurotoxicity Syndromes/etiology, Zika Virus, Insect Vectors, 3. Good health, Pesticide, Culicidae/drug effects, Culicidae, Larva, Pyriproxyfen, Toxicity testing, Microcephaly, Neurotoxicity Syndromes, Developmental neurotoxicity, Systems biology, Protein Interaction Maps/drug effects, Signal Transduction |
| Beschreibung: | 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. |
| Publikationsart: | Article |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2018.02.014 |
| Zugangs-URL: | https://europepmc.org/articles/pmc6087490?pdf=render https://pubmed.ncbi.nlm.nih.gov/29476864 https://pubmed.ncbi.nlm.nih.gov/29476864/ https://www.ncbi.nlm.nih.gov/pubmed/29476864 https://www.sciencedirect.com/science/article/pii/S0041008X18300607 https://europepmc.org/article/MED/29476864 https://www.cabdirect.org/cabdirect/abstract/20193204366 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087490 https://findresearcher.sdu.dk:8443/ws/files/137909177/A_systems_biology_approach_to_predictive_developmental_neurotoxicity_of_a_larvicide_used_in_the_prevention_of_Zika_virus_transmission.pdf https://portal.findresearcher.sdu.dk/da/publications/d092a28d-7cd5-451a-95e5-a7a4d2e8affa https://doi.org/10.1016/j.taap.2018.02.014 |
| Rights: | Elsevier TDM CC BY NC ND |
| Dokumentencode: | edsair.doi.dedup.....3fe1bc4e6d8a0627fe5dc5dd4b3b6c62 |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | 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. |
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| ISSN: | 0041008X |
| DOI: | 10.1016/j.taap.2018.02.014 |