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oai:docta.ucm.es:20.500.14352/972862025-04-01T00:02:24Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Martínez Caballero, María Aranzazu author Rodríguez, José Luis author López Torres, Bernardo author Martínez Caballero, Marta author Martínez Larrañaga, María Rosa author Anadón Navarro, Arturo Ramón author Ares Lombán, Irma author 2019 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. 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. 0013-9351 10.1016/j.envres.2019.108579 https://hdl.handle.net/20.500.14352/97286 1096-0953 https://doi.org/10.1016/j.envres.2019.108579 31330490 Oxidative stress and related gene expression effects of cyfluthrin in human neuroblastoma SH-SY5Y cells: Protective effect of melatonin