Neurotoxicity associated with oxidative stress and inflammasome gene expression induced by allethrin in SH-SY5Y cells

Author:

Castillo Giovana1,Barrios-Arpi Luis2,Ramos-Gonzalez Mariella3,Vidal Paola2,Gonzales-Irribarren Alejandro4,Ramos-Cevallos Norma1,Rodríguez José-Luis45

Affiliation:

1. Faculty of Pharmacy and Biochemistry, Research Institute Juan de Dios Guevara, Universidad Nacional Mayor de San Marcos, Lima, Peru

2. Animal Phisiology Laboratory, Faculty of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru

3. Zootechnics and Animal Production Laboratory, Faculty of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru

4. Pharmacology and Toxicology Laboratory, Faculty of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru

5. Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Universidad Complutense de Madrid, Madrid, Spain

Abstract

Pyrethroids, including allethrin, have largely been used as commercial insecticides. The toxicity of allethrin is little known, but it is assumed that, as occurs with other pyrethroids, it could cause alterations of the nervous system and pose both occupational and non-occupational health hazards. To evaluate the neurotoxicity of allethrin we used the MTT assay of SH-SY5Y neuroblastoma cells to determine cell viability. Dose-dependent reductions of cell viability served to compare the vehicle-group and the IC50 for allethrin, which was 49.19 μM. ROS production increased significantly at concentrations of 10–200 μM of allethrin, and NO levels were significantly increased by the effect of allethrin at a minimum concentration of 50 μM. Lipid peroxidation increased by the effect of allethrin at concentrations of 25, 50, 100, and 200 μM. Caspase 3/7 activity was induced by allethrin concentrations of 50, 100, and 200 μM. Here, we suggest that allethrin might affect the inflammasome complex (Caspase-1, NLRP3, and PYDC1) and apoptosis (Bax and Bcl-2) gene expression by mRNA fold change expression levels shown in Caspase-1 (2.46-fold), NLRP3 (1.57-fold), PYDC1 (1.48-fold), and Bax (2.1-fold). These results demonstrated that allethrin induced neurotoxicity effects on SH-SY5Y cells through activation of inflammasome pathways, cell death, and oxidative stress.

Funder

Universidad Nacional Mayor de San Marcos

Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health,Toxicology

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