Study of Pathobiochemistry of Catecholamine Cardiotoxicity: Role of Free Iron Ions and Their Chelation as a Possibility of Pharmacological Cardioprotec-tion.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Pavlína HAŠKOVÁ Supervisor: doc. PharmDr. Tomáš ŠIMŮNEK, Ph.D. Title of Doctoral Thesis: Study of pathobiochemistry of catecholamine cardiotoxicity: Role of free iron ions and their chelation as a possibility of pharmacological cardioprotec- tion. Catecholamine cardiotoxicity is known for a long time, but its patho- genesis is still incompletely understood. Although traditionally attributed to excessive β-adrenergic stimulation, there is a hypothesis that the catecholamine- induced cardiac cell damage includes involvement of oxidation products of catecholamines, which may arise due to spontaneous oxidation of catechola- mines under aerobic conditions. Spontaneous oxidation of catecholamines is a sequence of redox reactions leading to the formation of numerous reactive in- termediates, such as o-semiquinones and o-quinones, including aminochromes that are subject to redox cyclization generating reactive oxygen species (ROS). The generated ROS and aminochromes are toxic for cells. In addition, the autooxidation may be catalyzed by transition metals, which suggests that free intracellular iron (Fe) ions - the most abundant transition metal in the body - can promote not only the Haber-Weiss..