engleski

1-Phenacylpyridinium-4-aldoxime chloride is cytotoxic to SH-SY5Y neuroblastoma cell line

Pyridinium aldoximes are pharmacologically important nucleophylic agents acting as effective antidotes against poisoning by organophosphorous compounds which inhibit acetylcholinesterase (AChE ; EC 3.1.1.7.). Some 1-phenacylpyridinium compounds are AChE reversible inhibitors thus protecting it against certain organophosphorous poisons. Despite their complex actions on the cholinergic and adrenergic nervous system and a strong anticholinesterase effect, metabolic and cytotoxic effects of 1-phenacylpyridinium aldoximes derivatives have been poorly studied in vitro. In this study, the cytotoxicity of 1-phenacylpyridinium-4-aldoxime (FEPA-4) chloride was analyzed in SH-SY5Y neuroblastoma cell line, highly expressing acetylcholinesterase. SH-SY5Y cells were grown in MEM medium supplemented with 10% fetal bovine serum till treatment. Cells were incubated in 0.5 mM, 1 mM, 2 mM and 4 mM FEPA-4 in serum-free medium for 1, 3, 6, 12 and 24 hours. Changes in cellular morphology and cell viability were analyzed in native and hemalaun-eosin stained FEPA-4 treated vs. non-treated cell populations, by invert light microscopy. Results showed both concentration- and time-dependent effects of FEPA-4 to neuroblastoma cells in comparison with control cells. The observations were as follows: (1) 0.5 mM FEPA-4 did not influence cellular proliferation ability ; however slight alterations in cellular morphology appeared after 12 hours of incubation. (2) 1 mM FEPA-4 inhibiting effects to cellular proliferation, a decrease of cell number and morphological aberrations (rounded cell bodies, exudation of cytoplasmic elements, cell fragmentation) were first observed after 3 hours of incubation and proportionally more after 6, 12 and 24 hours. Hemalaun-eosin staining revealed that majority of cells was dead after 24 hours of treatment, with rounded cell bodies containing only nuclei surrounded by cytoplasmic remnants. (3) 2 mM and 4 mM FEPA-4 effects were tested after 24 hours of exposure and showed these concentrations were too high for chosen cellular model as cell number dropped dramatically due to massive cell death, revealed by microscopic analysis of native and hemalaun-eosin stained cells. The study shows in vitro toxicity of FEPA-4 to SH-SY5Y cell line. However, the exact mechanism of observed FEPA-4 toxicity and possible involvement of FEPA-4 action to acetylcholinesterase is being further explored in this cellular model.

1-Phenacylpyridinium-4-aldoxime chloride; neuroblastoma cell line; cytotoxicity

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