Pyrethroid Pesticides Inhibit Nerve Growth Factor and Laminin-1 Mediated Neurite Outgrowth

Insecticides inhibit or over-excite insect nerve impulses thereby killing these agricultural pests. Unfortunately these neurotoxins are also toxic to humans. Recently a new class of insecticides, the pyrethroids, have shown effective insecticidal activity with greatly reduced toxicity to human systems. Here we address the concern that at sub-lethal levels, the pyrethroids may exhibit developmental neurotoxicity in mammals. To assess this concern, studies were conducted with pyrethroid bifenthrin, showing inhibition of neurite outgrowth formation in NGF dependent PC12 cells. In order to further the investigation of pyrethroids as developmental neurotoxins, we investigated additional pyrethroids such as permethrin, cypermethrin, deltamethrin and esfenvalerate and extended these observations to laminin mediated neurite outgrowth in Neuro 2a cells. We found that the pyrethroid pesticides showed maximum inhibition of neurites at highest concentration of 10-5M in PC12 and Neuro 2a cells and almost no effect at 10-9 M concentration. Cypermethrin had the greatest inhibitory effect showing 2.0% neurites at 10-5 M concentration and permethrin showed the least inhibitory effect with 8.1% neurites in PC12 cells. Bifenthrin had the greatest inhibitory effect showing only 2.6% neurites at 10-5M concentration and permethrin showed the least inhibitory effect with 3.7% neurites in Neuro 2a cells. These inhibitions were observed in the absence of cell death as determined by the adherent ability of the cells and trypan blue exclusion assay. These data show that pyrethroid pesticides inhibit neurite outgrowth suggesting their generalized effect on neurite formation. This raised the possibility of these pyrethroid pesticides acting as developmental neurotoxins.