RT Journal Article
T1 Toxicologic evidence of developmental neurotoxicity of type II pyrethroids cyfluthrin and alpha-cypermethrin in SH-SY5Y cells
A1 Martínez Caballero, María Aranzazu
A1 López Torres, Bernardo
A1 Rodriguez, J.L.
A1 Martínez Caballero, Marta
A1 Maximiliano Guerra, Jorge Enrique
A1 Martínez Larrañaga, María Rosa
A1 Anadón Navarro, Arturo Ramón
A1 Ares Lombán, Irma
AB We attempted to identify cellular mechanisms as an approach to screen chemicals for the potential to cause developmental neurotoxicity. We examine, in SH-SY5Y cells, whether apoptosis and oxidative stress via reactive oxygen species (ROS) generation, caspase 3/7 activation, gene expression (Bax, Bcl-2, Casp-3, BNIP3, p53 and Nrf2) alterations and necrosis by release of cytosolic adenylate kinase (AK), underlie direct effects of the pyrethroids cyfluthrin and alpha-cypermethrin. We also determined transcriptional alterations of genes (TUBB3, NEFL, NEFH, GAP43, CAMK2A, CAMK2B, WNT3A, WNT5A, WNT7A, SYN1 and PIK3C3) linked to neuronal development and maturation. Our results indicate that cyfluthrin and alpha-cypermethrin have the ability to elicit concentration-dependent increases in AK release, cellular ROS production, caspase 3/7 activity and gene expression of apoptosis and oxidative stress mediators. Both pyrethroids caused changes in mRNA expression of key target genes linked to neuronal development. These changes might reflect in a subsequent neuronal dysfunction. Our study shows that SH-SY5Y cell line is a valuable in vitro model for predicting development neurotoxicity. Our research provides evidence that cyfluthrin and alpha-cypermethrin have the potential to act as developmental neurotoxic compounds. Additional information is needed to improve the utility of this in vitro model and/or better understand its predictive capability.
PB ELSEVIER SCI LTD
SN 0278-6915
YR 2020
FD 2020-03
LK https://hdl.handle.net/20.500.14352/97442
UL https://hdl.handle.net/20.500.14352/97442
LA eng
NO Martínez MA, Lopez-Torres B, Rodríguez JL, Martínez M, Maximiliano JE, Martínez-Larrañaga MR, Anadón A, Ares I. Toxicologic evidence of developmental neurotoxicity of Type II pyrethroids cyfluthrin and alpha-cypermethrin in SH-SY5Y cells. Food Chem Toxicol. 2020 Mar;137:111173. doi: 10.1016/j.fct.2020.111173. Epub 2020 Feb 3. PMID: 32028016.
NO Ministerio de Economía, Industria y Competitividad
DS Docta Complutense
RD 9 abr 2025