Cytoprotection by Melatonin, Precursors and Metabolites in an In Vitro Model of Neurotoxicity Induced by Okadaic Acid

I.      Tunez; R.      Drucker-Colin; M.   C.   Munoz; P.      Montilla

Abstract

Recently, it has been emphasized that oxidative stress could play a synergistic role with tau phosphorylation, cell shape changes, cytoskeletal disruption and cell death in Alzheimers disease. Okadaic acid induces oxidative damage, cell shape alterations, tau hyperphosphorylation and cytoskeletal disorganization similar to Alzheimers disease. In this sense, different evidence suggests that indolamines may be useful for protection against oxidative stress and cellular disorganization. In this study, we looked at the effects of melatonin, 5-hydroxytryptophan (5OHTrp), 5-hydroxytryptamine (5HT), N-acetyl-5- hydroxytryptamine (NA5OHT) or 6-hydroxymelatonin (6OHMEL) (10-5 M) on the oxidative changes and cell shape alterations produced by okadaic acid (50 nM) in N1E-115 neuroblastoma cells. The effects of okadaic acid were evaluated as changes in the quantity of lipid peroxidation products, reduced glutathione (GSH) content, activity of anti-oxidative enzymes and major length axes (as an index of cell shape changes). Okadaic acid gives rise to lipid peroxidation products (P < 0.001), GSH consumption (P < 0.001), major length axis (P < 0.001) and a reduction in the activity of GSH-transferase, GSH-reductase and catalase between 43.33 - 55.17%. These changes were completely prevented by melatonin, whereas 5OHTrp, 5HT, NA5OHT and 6OHMEL partially blocked the alterations induced by okadaic acid. In conclusion, our data indicates: (i) The importance of oxidative stress in both this experimental model and in the development and course of neurodegenerative diseases, especially Alzheimers. (ii) The protective effects of indolamines (iii) and that melatonin is much more efficient than its precursors and metabolites in reducing the extent of oxidative stress and cell shape changes induced by okadaic acid.

Keywords: alzheimers disease, cell shape, okadaic acid, oxidative stress, ne neuroblastoma cells

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