@misc{Pomierny_Bartosz_Sebastian_Evaluation_2015, author={Pomierny, Bartosz Sebastian}, address={Kraków}, howpublished={online}, year={2015}, school={Wydział Farmaceutyczny. Uniwersytet Jagielloński. Collegium Medicum.}, language={pol}, abstract={Ethylene glycol ethers (EGEs) due to their favorable physicochemical properties are widely used as ingredients in many household preparations, paints, coatings and medical products. Because the exposure to EGEs is high and, so far, there were no data concerning their influence on the mammalian cells of the central nervous system (CNS), thus the aim of this study was to evaluate, in the in vivo and in vitro model, potential, neurotoxic action of these compounds. In the in vivo model, we evaluated the influence of 4-week administration of 2-ethoxyethanol, 2-butoxyethanol and 2-phenoxyethanol (PHE), on the markers of oxidative stress and apoptosis in the rats frontal cortex and hippocampus. In in vitro studies, on SH-SY5Y cells, we determined the impact of EGEs and their metabolites on cells viability, level of released lactate dehydrogenase (necrosis), caspase-3 activity, and the mitochondrial membrane potential (apoptosis). To determine the intracellular mechanism of the toxicity of PHE and its metabolite, we investigated the influence of specific inhibitors of protein kinases on cytotoxic and proapoptotic effects of EGE and its metabolite. For this research we have chosen kinase inhibitors such as inhibitors of GSK-3β, p38-MAPK, JNK-MAPK, PLC.In vivo results of this study suggest that EGEs with lipophilic properties exert toxic influence on the CNS cells through raised oxidative stress and activated apoptosis.In vitro results indicate that the cytotoxic and proapoptotic effect of EGEs and metabolites may stem from their impact on many intracellular signal transduction pathways, mainly GSK3β, p38, JNK.We can conclude that long-term exposure to EGEs might be one of the reasons for the raised prevalence to neurodegenerative diseases.}, title={Evaluation of the neurotoxic activity of ethylene glycol ethers – in vitro and in vivo research}, type={Praca doktorska}, keywords={ethylene glycol ethers, alkoxyacetic acids, neurotoxicity, apoptosis, oxidative stress}, }