Romero Martínez, Manuel AlejandroRamos Alonso, EvaAres Lombán, IrmaCastellano Santos, Víctor JesúsMartínez Caballero, MartaMartínez Larrañaga, María RosaAnadón Navarro, Arturo RamónMartínez Caballero, María Aranzazu2024-02-012024-02-012017Romero A, Ramos E, Ares I, Castellano V, Martínez M, Martínez-Larrañaga MR, Anadón A, Martínez MA. Oxidative stress and gene expression profiling of cell death pathways in alpha-cypermethrin-treated SH-SY5Y cells. Arch Toxicol. 2017 May;91(5):2151-2164. doi: 10.1007/s00204-016-1864-y. Epub 2016 Oct 4. PMID: 27704156.0340-576110.1007/s00204-016-1864-yhttps://hdl.handle.net/20.500.14352/97730In this study, we investigated the induction of oxidative stress and apoptosis in human neuroblastoma cell line SH-SY5Y in response to alpha-cypermethrin (α-CYPER) exposure. MTT and LDH assays were carried out to assess the α-CYPER cytotoxicity. The IC50 value for α-CYPER was calculated to be 78.3 ± 2.98 µM for the MTT assay and 71.5 ± 3.94 µM for LDH assay. The pyrethroid α-CYPER (1-100 µM), in a dose-dependent manner, induced a significant increase in lipid peroxides measured as malondialdehyde (MDA) and in the levels of nitric oxide (NO). The neuroprotective role of three antioxidants, melatonin (MEL), Trolox and N-acetylcysteine (NAC) against α-CYPER-induced oxidative stress was examined. Compared to other antioxidants, MEL (1 µM) treatment showed the most effective protection against α-CYPER-induced lipid peroxidation and NO production. The effects of α-CYPER on gene expression profiling of cell death pathway in human neuroblastoma SH-SY5Y cells were also investigated. Of the 84 genes examined (P < 0.001; fold change >1.5), changes in mRNA levels were detected in 39 genes: 36 were up-regulated and 3 were down-regulated. A greater fold change reversion than 3.5-fold was observed on the up-regulated ATP6V1G2, BCL2, CASP9, FAS, GADD45A, SPATA2, SYCP2, ATG7, NFKB1, SNCA, ULK1 and JPH3 genes. The results demonstrated that α-CYPER alters the expression of apoptosis-, autophagy- and necrosis genes as well as induces oxidative stress which may lead to DNA damage. The detailed knowledge of the changes in gene expression obtained will provide a basis for further elucidating the molecular mechanisms of the α-CYPER-induced toxicity.engjournal articlehttps://doi.org/10.1007/s00204-016-1864-y27704156restricted access615.9Cell death pathwaysMelatonin neuroprotectionMicroarrayNeurotoxicitySH-SY5Y cellsα-CypermethrinCiencias Biomédicas3214 Toxicología