Characterization of boscalid-induced oxidative stress and neurodevelopmental toxicity in zebrafish embryos

Wang, Honglei; Meng, Zhen; Liu, Fasheng; Zhou, Liqun; Su, Meile; Meng, Yunlong; Zhang, Shouhua; Liao, Xinjun; Cao, Zigang; Lu, Huiqiang

doi:10.1016/j.chemosphere.2019.124753

Cited by 69 publications

(35 citation statements)

References 41 publications

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“…Several studies have reported that a number of SDHIs cause neurotoxicity (Wang et al, 2020; Yao et al, 2018). We investigated the effect of bixafen exposure on the development of the central nervous system.…”

Section: Resultsmentioning

confidence: 99%

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: Resultsmentioning

confidence: 99%

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 mechanism of action is still under investigation, but it appears it specifically inhibits the mitochondria of mites [13]. Boscalid is a commonly used fungicide that is considered nontoxic to terrestrial animals [12]; though, a basic science investigation suggested it can contribute to neurodevelopmental toxicity via oxidative stress [14].…”

Section: Discussion On Pesticide Componentsmentioning

confidence: 99%

E-Cigarette, or Vaping, Product Use Associated Lung Injury (EVALI) with Acute Respiratory Failure in Three Adolescent Patients: a Clinical Timeline, Treatment, and Product Analysis

et al. 2020

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Introduction E-cigarette, or vaping, product use associated lung injury (EVALI) has become a recent concern among public health officials. Factors that contribute to the concern include an increasing number of cases over time, the severity of the illness, and an unknown understanding of the pathophysiology and etiology of the illness. Case Series We cared for three adolescent patients with acute respiratory failure secondary to EVALI. All three patients were treated with high-dose steroids in addition to antimicrobials, which resulted in clinical improvement and resolution of their respiratory failure. Pulmonary function testing was performed on these previously healthy patients both acutely and subacutely. Additionally, we report the results from the laboratory analysis of one vaping device fluid which revealed previously unpublished components within these products. Discussion EVALI is a recent public health concern without a known etiology which can cause life-threatening lung injury in patients without prior lung pathology. We hope these cases will highlight the importance of return precautions in adolescents with vague respiratory symptoms and provide a cautionary tale to providers while they counsel patients regarding the use of these products.

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“…While the tissue culture flasks and culture plates were obtained from Falcon / Fred Baker (Runcorn, Cheshire, England), gentamicin was obtained from Ibrahim Etem (20 mg Genta ® bulb, Ibrahim Etem, Istanbul, Turkey). [7,10]…”

Section: Supplies and Chemicalsmentioning

confidence: 99%

“…Ten different areas with approximately 10 cells were selected for pesticides and controls. [7] By automatically measuring the total neurite length (in pixels) for cells in each area, the results were expressed as the average neurite length per cell. [1,10,12,21] Oxidative Stress Cells were immunostained for e-NOS and i-NOS to evaluate levels of the oxidative stress.…”

Section: Cell Differentiation and Neurite Outgrowthmentioning

confidence: 99%

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Investigation of the moderate toxicity of agricultural pesticides cyantraniliprole, boscalid and spiromesifen in vitro using neurotoxicity screening test

KARAKAYALI¹,

Kekeç²,

Önal³

et al. 2021

Anatomy

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Objectives: Although industrial products used as agricultural pesticides are considered safe, they are likely to lead to chronic problems due to their long-term effects. The neurotoxicity screening test (NST) is a method based on the inhibition of neurite extension of neurons that do not not die with toxic effects. In this study, we aimed to investigate the moderate neurotoxic effects and reveal the potential dangers of agricultural pesticides in vitro using NST. Methods: Cyantraniliprole, boscalid and spiromesifen were used as agricultural pesticides on the mouse neuroblastoma cell line N2a. Neurite extension of neurons was performed by taking them into the proliferation medium followed by the differentiation medium. Cell viability and proliferation were analyzed using the MTT test. The percentage of neurite inhibition was calculated by measuring neurite outgrowth by NST. Oxidative stress was analyzed by NOS staining with h-score and apoptosis was shown using the apoptotic index in TUNEL staining. Results: Cyantraniliprole, boscalid and spiromesifen at high concentrations caused neurite inhibition, decreased proliferation and reduced the viability of cultured neurons. These agricultural pesticides were found to be significantly moderate toxic for neurons by increasing oxidative stress and apoptosis. Conclusion: We conclude neurite inhibition may be important in early recognition for detecting and preventing the neurotoxic effect of pesticides, and NST is an important in vitro test that can predict the long-term effects of neurotoxic agents. In the present study, we observed cyantraniliprole, boscalid and spiromesifen had moderate neurotoxic effects in varying degrees using NST. This means that pesticides may behave toxic even in permissible limits for chronic exposure.

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Characterization of boscalid-induced oxidative stress and neurodevelopmental toxicity in zebrafish embryos

Cited by 69 publications

References 41 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

E-Cigarette, or Vaping, Product Use Associated Lung Injury (EVALI) with Acute Respiratory Failure in Three Adolescent Patients: a Clinical Timeline, Treatment, and Product Analysis

Investigation of the moderate toxicity of agricultural pesticides cyantraniliprole, boscalid and spiromesifen in vitro using neurotoxicity screening test

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