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

Toxics

Luis Barrios-Arpi¹  Yurie Arias¹  Bernardo Lopez-Torres²  José-Luis Rodríguez²  Giulio Ticli³  Ennio Prosperi³  Mariella Ramos-Gonzalez⁴ 

[1] Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 41, Peru;Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain;Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, CNR, 27100 Pavia, Italy;Zootecnia an Animal Production Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 41, Peru;

关键词: flumethrin;    oxidative stress;    apoptosis;    neurotoxicity;    SH-SY5Y cells;   

DOI  :  10.3390/toxics10030131

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown