Study of selected iron chelators for oxidative stress prevention in PC12 cell line

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Pavel Homola Supervisor: doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of selected iron chelators for oxidative stress prevention in PC12 cell line Parkinson's disease is a progressive neurodegenerative disease with motoric symptoms (tremor, rigidity, akinesia, postural disorders), which are connected with the loss of dopaminergic neurons in Substantia nigra pars compacta. Oxidative stress has been associated with patological processes of PD as an initiator or a member of patological cascades. Morover, oxidative stress plays a role in development of several diseases, e.g. cardiovascular disorders. Damages caused by oxidative stress are based on reactive oxidative species (ROS). The most common and the most toxic compound is hydroxyl radical, which is created by chemical reaction with iron as a catalyst (Fenton reaction). Iron chelators act as protectors against oxidative harm in tissues. They chelate iron ions, therefore prevent their catalytic activity and formation of ROS. This study deals with the determination of cytotoxicity and protective effects of clinically used iron chelators (deferoxamine - DFO, deferiprone - L1, deferasirox - ICL670A) in PC12 cell line as..