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.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Sidiropoulou E,Sachana M,Flaskos J,Harris W,Hargreaves AJ,Woldehiwet Z

doi

10.1016/j.toxlet.2010.12.009

subject

Has Abstract

pub_date

2011-02-25 00:00:00

pages

86-91

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(10)01797-2

journal_volume

201

pub_type

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