Bifenthrin causes neurite retraction in the absence of cell death: A modelfor pesticide associated neurodegeneration.
Avishek Nandi, Daljit Chandi, Rethabile Lechesa, Stephen C. Pryor, Ashlea McLaughlin, Josephine A. Bonventre, Katherine Flynn, Benjamin S. Weeks
Med Sci Monit 2006; 12(5): BR169-173
Background: Bifenthrin is a synthetic pyrethroid insecticide derivativeof naturally occurring pyrethrins from chrysanthemum flowers. Bifenthrin is considered relatively safeand therefore incorporated as the active ingredient in preparations sold over the counter for householduse. Recent studies have raised concern that chronic exposure to pesticides in the home setting may increasethe risk for neurodegenerative diseases. To address this concer, in the present study, bifenthrin isadded to pre-differentiated PC12 and effect of bifenthrin on the retraction of existing neurites is observeda model for neurodegeneration. Material/Methods: PC12 cells were differentiated with nerve growth factorfor twenty-four hours and then treated with what was determined to be a sublethal dose of bifenthrinfor up to an additional 48 hours. The percent of cells with neurites was assessed at various times beforeand after nerve growth factor treatment. Bifenthrin toxicity was determined using trypan blue exclusion.Results: Bifenthrin was not toxic to PC12 cells at concentrations ranging from 1x10[sup]-10[/sup] M to 1x10[sup]-4[/sup]M. Twenty-four hours after nerve growth factor treatment, a maximum percent of cells had formed neuritesand with a treatment of 1x10[sup]-5[/sup] M bifenthrin, approximately 80% of these neurites retracted in within12 additional hours and almost all neurites had retracted within 48 hours. Trypan exclusion showed thatthese cells were viable. Conclusions: These data show that bifenthrin can stimulate the retraction ofneurites in the absence of frank toxicity.
Keywords: Cell Survival - drug effects, Pyrethrins - toxicity, PC12 Cells, Neurons - pathology, Neurites - pathology, Nerve Growth Factor - pharmacology, Nerve Degeneration - pathology, Models, Neurological, Lindane - toxicity, Insecticides - toxicity, Animals, Rats