Toxicologic evidence of developmental neurotoxicity of Type II pyrethroids cyfluthrin and alpha-cypermethrin in SH-SY5Y cells

Martínez, María Aránzazu; López-Torres, Bernardo; Rodrı́guez, José Luis; Martínez, Marta; Maximiliano, Jorge-Enrique; Martínez-Larrañaga, María Rosa; Anadón, Arturo; Arés, Irma

doi:10.1016/j.fct.2020.111173

Cited by 31 publications

(14 citation statements)

References 42 publications

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“…These findings allow us to demonstrate that flumethrin may exert cell death effects involving apoptosis. These results are comparable with other studies that evaluated the effects of alpha-cypermethrin and cyfluthrin on the expression of a wide variety of pro-apoptotic molecules including caspase-3 and Bax, important endogenous regulators of cellular activity in response to a wide variety of physiological and pathological injuries [ 25 , 26 , 33 , 45 ].…”

Section: Discussionsupporting

confidence: 88%

“…Oxidative stress has been postulated to be one of the most important issues in insecticide toxicology [ 25 , 28 , 29 , 30 ]. Several in vitro studies have shown the potential ability of pyrethroids to produce oxidative stress [ 25 , 26 , 31 , 32 , 33 ]. The present study showed that SH-SY5Y neuroblastoma cells treated with flumethrin (1–1000 μM) in a dose-dependent manner produced a significant cellular ROS formation.…”

Section: Discussionmentioning

confidence: 99%

“…Our study found that SH-SY5Y neuroblastoma cells exposed to flumethrin (at 50 μM, the lowest effective dose) produced a significant increase in ROS (37% with respect to the control). Martínez et al (2020) [ 33 ] reported that the 2.5 μM dose of cyfluthrin and the 5 μM dose of alpha-cypermethrin increased ROS generation by 22% and 24%, respectively. This marked difference could be related to a less toxic effect of flumethrin, 20 times less than cyfluthrin and 10-fold less than cypermethrin.…”

Section: Discussionmentioning

confidence: 99%

“…We show that caspase 3/7 activity was significant for the effect of flumethrin at 20 (10%), 50 (24%), 100 (34%), 200 (37%), 500 (42%), and 1000 (42%) µM doses. A study reported by Martínez et al (2020) [ 33 ] showed that cypermethrin (25 µM) and cyfluthrin (2.5 µM) induced caspase 3/7 activity by 22% and 24% relative to the control, respectively. Furthermore, other non-pyrethroid pesticides such as glyphosate (5 mM, 71%) and its metabolite (10 mM, 78%) produced increased caspase 3/7 activity in SH-SY5Y cells [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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In Vitro Neurotoxicity of Flumethrin Pyrethroid on SH-SY5Y Neuroblastoma Cells: Apoptosis Associated with Oxidative Stress

Barrios-Arpi

Arias

López-Torres

et al. 2022

Toxics

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Pyrethroids are neurotoxicants for animals, showing a pattern of toxic action on the nervous system. Flumethrin, a synthetic pyrethroid, is used against ectoparasites in domestic animals, plants, and for public health. This compound has been shown to be highly toxic to bees, while its effects on other animals have been less investigated. However, in vitro studies to evaluate cytotoxicity are scarce, and the mechanisms associated with this effect at the molecular level are still unknown. This study aimed to investigate the oxidative stress and cell death induction in SH-SY5Y neuroblastoma cells in response to flumethrin exposure (1–1000 µM). Flumethrin induced a significant cytotoxic effect, as evaluated by MTT and LDH leakage assays, and produced an increase in the biomarkers of oxidative stress as reactive oxygen species and nitric oxide (ROS and NO) generation, malondialdehyde (MDA) concentration, and caspase-3 activity. In addition, flumethrin significantly increased apoptosis-related gene expressions (Bax, Casp-3, BNIP3, APAF1, and AKT1) and oxidative stress and antioxidative (NFκB and SOD2) mediators. The results demonstrated, by biochemical and gene expression assays, that flumethrin induces oxidative stress and apoptosis, which could cause DNA damage. Detailed knowledge obtained about these molecular changes could provide the basis for elucidating the molecular mechanisms of flumethrin-induced neurotoxicity.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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In Vitro Neurotoxicity of Flumethrin Pyrethroid on SH-SY5Y Neuroblastoma Cells: Apoptosis Associated with Oxidative Stress

Barrios-Arpi

Arias

López-Torres

et al. 2022

Toxics

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“…The organophosphorous insecticide chlorpyrifos has been implicated as developmental neurotoxicant both in vivo and in vitro (Rauh et al 2012 ; Slotkin and Seidler 2012 ). The developmental neurotoxic potential of pyretroids has recently been demonstrated on SH-SY5Y cells (Martinez et al 2020 ). The pesticide rotenone, a mitochondrial electron transport chain blocker, is known for its adverse effect on dopaminergic neurons (Betarbet et al 2000 ; Pamies et al 2018 ), and is thus often used in Parkinson disease research (Heinz et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System

Schmitz¹,

Dempewolf²,

Tan³

et al. 2021

Neurotox Res

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Pesticide exposure during in utero and early postnatal development can cause a wide range of neurological defects. However, relatively few insecticides have been recognized as developmental neurotoxicants, so far. Recently, discovery of the insecticide, fipronil, in chicken eggs has raised public concern. The status of fipronil as a potential developmental neurotoxicant is still under debate. Whereas several in vivo and in vitro studies suggest specific toxicity, other in vitro studies could not confirm this concern. Here, we tested fipronil and its main metabolic product, fipronil sulfone both at concentrations between 1.98 and 62.5 µM, alongside with the established developmental neurotoxicant, rotenone (0.004–10 µM) in vitro on the human neuronal precursor cell line NT2. We found that rotenone impaired all three tested DNT endpoints, neurite outgrowth, neuronal differentiation, and precursor cell migration in a dose-dependent manner and clearly separable from general cytotoxicity in the nanomolar range. Fipronil and fipronil sulfone specifically inhibited cell migration and neuronal differentiation, but not neurite outgrowth in the micromolar range. The rho-kinase inhibitor Y-27632 counteracted inhibition of migration for all three compounds (EC50 between 12 and 50 µM). The antioxidant, n-acetyl cysteine, could ameliorate the inhibitory effects of fipronil on all three tested endpoints (EC 50 between 84 and 164 µM), indicating the involvement of oxidative stress. Fipronil sulfone had a stronger effect than fipronil, confirming the importance to test metabolic products alongside original pesticides. We conclude that in vitro fipronil and fipronil sulfone display specific developmental neurotoxicity on developing human model neurons.

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Synthetic organic chemicals (flame retardants and pesticides) with neurotoxic potential induced behavioral impairment on zebrafish (Danio rerio): a non-invasive approach for neurotoxicology

Ren

Poopal

Ramesh

2021

Environ Sci Pollut Res

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Toxicologic evidence of developmental neurotoxicity of Type II pyrethroids cyfluthrin and alpha-cypermethrin in SH-SY5Y cells

Cited by 31 publications

References 42 publications

In Vitro Neurotoxicity of Flumethrin Pyrethroid on SH-SY5Y Neuroblastoma Cells: Apoptosis Associated with Oxidative Stress

In Vitro Neurotoxicity of Flumethrin Pyrethroid on SH-SY5Y Neuroblastoma Cells: Apoptosis Associated with Oxidative Stress

Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System

Synthetic organic chemicals (flame retardants and pesticides) with neurotoxic potential induced behavioral impairment on zebrafish (Danio rerio): a non-invasive approach for neurotoxicology

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