Biomarcadores de la respuesta celular al estrés oxidativo en presencia de antioxidantes en varios modelos celulares

Résumé

Nowadays, in our society an increasing interest on antioxidants exists. In this PhD thesis we will examine the effects of different antioxidants on cell viability and function, employing exocrine pancreatic cells, hippocampal astrocytes and AR42J tumor cells as cellular models. We will pay major attention to the changes induced by various antioxidants on cell viability, the cell cycle, Ca2+ homeostasis, mitochondrial physiology and the secretory processes.Melatonin and ebselen are the antioxidants chosen for this purpose. Melatonin does not exert deleterious effects on cell viability, whereas in the presence of ebselen a decrease in cell viability was observed in the cellular models in which it was tested. Moreover, melatonin and ebselen, at the concentrations evaluated and in the cellular models employed, depict opposite effects on Ca2+ homeostasis. Melatonin, itself, does not stimulate amylase release by pancreatic acinar cells, but reduces amylase secretion evoked by the pancreatic agonist CCK-8. No detectable changes in the mitochondrial parameters studied were observed in pancreatic acinar cells incubated with melatonin. Conversely, in astrocytes and AR42J cells, ebselen led to major changes in [Ca2+]m, in mitochondrial membrane potential, in mitochondrial membrane permeability and on mitochondrial network integrity, which could compromise their function. Therefore, we think that it is not possible by the moment to assume that antioxidants, any type, have beneficial effects on the body.