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Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis. stimulation autoxidation prooxidant pro oxidant species Nondifferentiated Non differentiated SHSY5Y SHSYY SH SY5Y SY Y ADRinduced induced neurotoxicity nerves 0.1, 01 0 1 (0.1 025 25 0.25 05 5 0. 1mM mM lactate LDH (LDH 34,5dimethylthiazol2yl2,5diphenyl 345dimethylthiazol2yl25diphenyl dimethylthiazolyldiphenyl 3 4,5 dimethylthiazol 2yl 2,5 diphenyl 4 2 yl MTT (MTT reduction timepoints time points 24, 24 (24 48 96h h . 96h) timedependent dependent 0.1mM 01mM (0.1mM Nacetylcysteine N acetyl cysteine 1mM, , (1mM) synthesis 05mM 5mM 025mM 25mM 96 exposure 100µM µM (100µM nonprotective. nonprotective non protective. protective non-protective conclusion nondifferentiated products catecholamineinduced analysis SHSY SYY 0.1 (0. 02 0.2 34 5dimethylthiazol2yl2 5diphenyl 45 4, 2, (2 (1mM 9 (0 dimethylthiazolyl 5dimethylthiazol2yl (