Martínez Caballero, María AranzazuRodríguez, José LuisLópez Torres, BernardoMartínez Caballero, MartaMartínez Larrañaga, María RosaAnadón Navarro, Arturo RamónAres Lombán, Irma2024-01-312024-01-312019Martínez MA, Rodríguez JL, Lopez-Torres B, Martínez M, Martínez-Larrañaga MR, Anadón A, Ares I. Oxidative stress and related gene expression effects of cyfluthrin in human neuroblastoma SH-SY5Y cells: Protective effect of melatonin. Environ Res. 2019 Oct;177:108579. doi: 10.1016/j.envres.2019.108579. Epub 2019 Jul 12. PMID: 31330490.0013-935110.1016/j.envres.2019.108579https://hdl.handle.net/20.500.14352/97286This study was designed to assess oxidative stress induction in human neuroblastoma SH-SY5Y cells in response to cyfluthrin exposure. Cell viability MTT assay was carried out to assess cyfluthrin cytotoxicity; IC30 and IC50 values for cyfluthrin were calculated to be 4.81 ± 0.92 μM and 19.39 ± 3.44 μM, respectively. Cyfluthrin induced a significant increase in ROS generation, lipid peroxides measured as malondialdehyde (MDA) and nitric oxide (NO) production and a significant decrease in NQO1 activity. The antioxidant activity of melatonin (MEL), Trolox, N-acetylcysteine (NAC) and Sylibin against cyfluthrin-induced oxidative stress was examined. Cyfluthrin increased significantly gene expressions of apoptosis, proinflammation and oxidative stress (Bax, Bcl-2, Casp-3, BNIP3, AKT1, p53, APAF1, NFκB1, TNFα and Nrf2) mediators. In the most genes, the mRNA levels induced by cyfluthrin were partially reduced by MEL (1 μM). Cyfluthrin effects on gene expression profiling of oxidative stress pathway by Real-Time PCR array analysis showed that of the 84 genes examined, (fold change > 1.5) changes in mRNA levels were detected in 31 genes: 13 upregulated and 18 down-regulated. A fold change>3.0 fold was observed on upregulated CYBB, DUOX1, DUOX2, AOX1, BNIP3, HSPA1A, NOS2, and NQO1 genes. The greater fold change reversion (2.5 fold) by MEL (1 μM) was observed on cyfluthrin-upregulated CYBB, AOX1, BNIP3 and NOS2 genes. These results demonstrated that oxidative stress is a key element in cyfluthrin induced neurotoxicity as well as MEL may play a role in reducing cyfluthrin-induced oxidative stress.engjournal article1096-0953https://doi.org/10.1016/j.envres.2019.10857931330490restricted access61CyfluthrinSH-SY5Y cellsNeurotoxicityOxidative stressMelatonin neuroprotectionCiencias Biomédicas3214 Toxicología