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

Luis Barrios-Arpi, Yurie Arias, Bernardo Lopez-Torres, Mariella Ramos-Gonzalez, Giulio Ticli, Ennio Prosperi, José Luis Rodríguez

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number131
Issue number3
StatePublished - Mar 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the (1) Project “PCONFIGI A20080661” from Universidad Nacional Mayor de San Marcos; (2) Project of Collaboration Nº 02-2021-Biennial-Programme 2021-2022 Consiglio Nazionale delle Ricerche, Istituto di Genetica Molecolare “Luca Cavalli-Sforza”, Pavia (CNR-Pavia, Italy) and National Council for Science-Technology and Technological Innovation (CONCYTEC-Peru); and (3) Lopez-Torres B was supported by PROCIENCIA-CONCYTEC Peru, grant number 122-2017-FONDECYT.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Apoptosis
  • Flumethrin
  • Neurotoxicity
  • Oxidative stress
  • SH-SY5Y cells


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