title: Fipronil interferes with the differentiation of mouse N2a neuroblastoma cells.
abstract: The purpose of this study was to evaluate the neurotoxic potential of the pesticide fipronil (FIP) towards the differentiation of mouse N2a neuroblastoma cells. At concentrations of 1, 5 and 10 μM that were not cytotoxic, as shown by two different cell viability assays, FIP impaired potently after 24h the development of axon-like processes, with a concentration of 1 μM causing 50% inhibition. Densitometric analysis of immunoblots of extracts of N2a cells exposed to FIP demonstrated that the axon-inhibitory action of the pesticide was not accompanied by significant changes in the levels of total and phosphorylated neurofilament heavy chain (NFH). FIP also induced no alteration in the levels of total and tyrosinated α-tubulin. On the other hand, this pesticide caused severe disruption of the developmentally important ERK 1/2-MAP kinase signal transduction pathway, as evidenced by significant reductions in the activation state of MAPK kinase (MEK 1/2) and, particularly, ERK 1/2. The above data seem to justify very recent concerns that FIP has the capacity to induce developmental neurotoxicity in mammals.
authors.affiliation: Department of Infection Biology, Institute of Infection & Global Health, University of Liverpool, Leahurst Campus, Leahurst, Neston, Wirral CH64 7TE, UK.
authors.forename: Erasmia
authors.initials: E
authors.lastname: Sidiropoulou
authors.forename: Magdalini
authors.initials: M
authors.lastname: Sachana
authors.forename: John
authors.initials: J
authors.lastname: Flaskos
authors.forename: Wayne
authors.initials: W
authors.lastname: Harris
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Hargreaves
authors.forename: Zerai
authors.initials: Z
authors.lastname: Woldehiwet
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D014411:Neoplastic Stem Cells; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D011720:Pyrazoles / Q000633:toxicity*; D014404:Tubulin / Q000378:metabolism
chemical_list: D007306:Insecticides; D016900:Neurofilament Proteins; D011720:Pyrazoles; D014404:Tubulin; D048049:Extracellular Signal-Regulated MAP Kinases; C082360:fipronil