RT Journal Article T1 Oxidative stress and related gene expression effects of cyfluthrin in human neuroblastoma SH-SY5Y cells: Protective effect of melatonin A1 Martínez Caballero, María Aranzazu A1 Rodríguez, José Luis A1 López Torres, Bernardo A1 Martínez Caballero, Marta A1 Martínez Larrañaga, María Rosa A1 Anadón Navarro, Arturo Ramón A1 Ares Lombán, Irma AB This 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. PB Elsevier SN 0013-9351 YR 2019 FD 2019 LK https://hdl.handle.net/20.500.14352/97286 UL https://hdl.handle.net/20.500.14352/97286 LA eng NO Martínez 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. NO Ministerio de Economía, Industria y Competitividad (España) DS Docta Complutense RD 30 jun 2025