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

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

doi:10.3390/toxics10030131

Abstract

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.

Highlights

Many widely used pesticides, such as carbamates, organochlorine-phosphates, and others, have been withdrawn or are being discontinued due to their high levels of toxicity and their negative effects on the environment
The IC50 value for flumethrin was calculated to be 104 μM (Figure 1A). We examined this cytotoxic effect of flumethrin by assessing Lactate Dehydrogenase (LDH) release
The SH-SY5Y cells incubated for a 24 h period with flumethrin at the doses of 50, 100, 200, 500, and 1000 μM produced significant elevations in LDH leakage (24%, 42%, 61%, 68%, and 110%, respectively) (Figure 1B) compared to vehicle-treated cells (Veh, negative control)

Summary

Introduction

Many widely used pesticides, such as carbamates, organochlorine-phosphates, and others, have been withdrawn or are being discontinued due to their high levels of toxicity and their negative effects on the environment. Synthetic pyrethroids are used instead due to their selective toxicity to various types of insects, lower toxicity to mammals, and less detrimental effects on the environment [1]. A natural purified extract of Chrysanthemum spp. flowers, has been used as a natural insecticide for long-term exposure. The active components of pyrethrum are known as pyrethrins [2]. The main way to classify pyrethroids (Type I and II) is based on the presence of the α-cyano group in their chemical structure; for example, Type II has this group present in its chemical structure. Synthetic pyrethroids are widely used in the control of pests that infest agriculture, livestock, residences, and against vectors that affect public health [6,7]

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