Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death

Brenet, Alexandre; Somkhit, Julie; Hassan-Abdi, Rahma; Yanicostas, Constantin; Romain, Christiane; Bar, Olivier; Igert, Alexandre; Saurat, Dominique; Taudon, Nicolas; Dal-Bo, Gregory; Nachon, Florian; Dupuis, Nina; Soussi-Yanicostas, Nadia

doi:10.1101/2019.12.15.876649

Cited by 2 publications

(2 citation statements)

References 54 publications

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“…Perinatal exposure of rats to organophosphorus pesticides alters brain morphometry (Veronesi and Pope, 1990). Similarly, our recent studies have shown that embryos exposed to organophosphorus pesticides showed neurodevelopmental disorders, including altered excitatory/inhibitory synapse balance (Brenet et al, 2019).…”

Section: Discussionmentioning

confidence: 87%

Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

Hassan-Abdi

Brenet

Soussi-Yanicostas

2020

Preprint

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Succinate dehydrogenase inhibitors (SDHIs) are the most widely used fungicides against plant parasitic fungi. They act by blocking the enzyme succinate dehydrogenase (SDH), a key component of mitochondrial respiration, which is highly conserved throughout evolution. Recently, it has been reported that some SDHIs used in many fungicides do not only inhibit the SDH activity of target fungi but can also block several non-target human cells in in vitro models. This study reveals a lack of SDHI species specificity and so points to a major health risk for exposed organisms, including humans. Despite the frequent detection of SDHIs in the environment and on harvested products and their increasing use in modern agriculture, their potential toxic effects in vivo, especially on neurodevelopment, are still under-evaluated. Here, we assessed the neurotoxicity of bixafen, one of the latest-generation SDHIs, which had never been tested during neurodevelopment. For this purpose, we used a well-known vertebrate model for toxicity testing, namely zebrafish transparent embryos, and live imaging using transgenic lines labelling the brain and spinal cord. Here we show that bixafen causes microcephaly and defects on motor neuron axon outgrowth and their branching during development. Our findings show that the central nervous system is highly sensitive to bixafen, thus demonstrating for the first time in vivo that an SDHI, bixafen, widely used in agriculture, is neurotoxic in vertebrates and causes neurodevelopmental defects. This work adds to our knowledge of the toxic effect of SDHIs on neurodevelopment and may help us take the appropriate precautions to ensure protection against the neurotoxic effects of these substances

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Section: Discussionmentioning

confidence: 87%

Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

Hassan-Abdi

Brenet

Soussi-Yanicostas

2020

Preprint

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“…The percentage of apoptosis in cells of zebrafish larvae is determined [25] using AO stain; a nucleic acid staining dye used to detect early stages of apoptosis. Apoptosis was studied in 96‐h zebrafish larvae using AO staining protocol.…”

Section: Methodsmentioning

confidence: 99%

Deacetylepoxyazadiradione Derived from Epoxyazadiradione of Neem (Azadirachta indica A. Juss) Fruits Mitigates LPS‐Induced Oxidative Stress and Inflammation in Zebrafish Larvae

Murugan

Rajesh

Guru

et al. 2022

Chemistry & Biodiversity

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Reactive oxygen species (ROS) produced by cell metabolism have a duplex role in oxidation and inflammation reactions which involve cell damage or repair responses. Excess ROS production has detrimental effects on the survival of cells. We examined the protective effect of a semi-natural compound NF2 (deacetylepoxyazadiradione), for its protective activity against free radical-mediated stress and inflammatory response to lipopolysaccharide (LPS) using zebrafish larvae. Preliminary antioxidant assays indicated an increase in scavenging of free radicals from NF2 than NF1 (Epoxyazadiradione) in a concentration-dependent manner. Cell cytotoxicity was determined using rat myoblast cell lines (L6), and more than 95 % of cell viability was obtained. Zebrafish developmental toxicity test indicated that NF2 is not toxic even at 150 μM. The percentage of ROS, lipid peroxidation, nitric oxide and apoptosis were reduced significantly in NF2 treated LPS-stressed zebrafish larvae. The reduced number of employed macrophages on NF2 treatment was observed in neutral red dyemarked macrophage localization images. Relative expression of antioxidant genes in zebrafish larvae after treatment with NF2 is significantly increased. The RT-PCR quantification of antioxidant and anti-inflammatory gene expression indicated decreased relative folds of pro-inflammatory cytokines, iNOS and increased relative folds of mitochondrial antioxidant genes (GR, GST and GPx) in LPS stressed zebrafish larvae after treatment with NF2. From the overall obtained results, it can be concluded that NF2 reduced the oxidative stress and inflammatory response by scavenging free radicals caused by LPS.

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Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death

Cited by 2 publications

References 54 publications

Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

Deacetylepoxyazadiradione Derived from Epoxyazadiradione of Neem (Azadirachta indica A. Juss) Fruits Mitigates LPS‐Induced Oxidative Stress and Inflammation in Zebrafish Larvae

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