Redox active metal-induced oxidative stress in biological systems |
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Authors: | Klaudia Jomova Stanislav Baros Marian Valko |
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Institution: | (1) Department of Chemistry, Faculty of Natural Sciences, Constantine The Philosopher University, 949 74 Nitra, Slovakia;(2) Faculty of Chemical and Food Technology, Slovak Technical University, 812 37 Bratislava, Slovakia |
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Abstract: | A number of studies performed on biological systems have shown that redox-active metals such as iron and copper as well as
other transition metals can undergo redox cycling reactions and produce reactive free radicals termed also reactive oxygen
species (ROS) or reactive nitrogen species (RNS). The most representative examples of ROS and RNS are the superoxide anion
radical and nitric oxide, respectively, both playing a dual role in biological systems. At low/moderate concentrations of
ROS and RNS, they can be involved in many physiological roles such as defense against infectious agents, involvement in a
number of cellular signaling pathways and other important biological processes. On the other hand, at high concentrations,
ROS and RNS can be important mediators of damage to biomolecules involving DNA, membrane lipids, and proteins. One of the
most damaging ROS occurring in biological systems is the hydroxyl radical formed via the decomposition of hydrogen peroxide
catalyzed by traces of iron, copper and other metals (the Fenton reaction). The hydroxyl radical is known to react with the
DNA molecule, forming 8-OH-Guanine adduct, which is a good biomarker of oxidative stress of an organism and a potential biomarker
of carcinogenesis. This review discusses the role of iron and copper in uncontrolled formation of ROS leading to various human
diseases such as cancer, cardiovascular disease, and neurological disorders (Alzheimer’s disease and Parkinson’s disease).
A discussion is devoted to the various protective antioxidant networks against the deleterious action of free radicals. Metal-chelation
therapy, which is a modern pharmacotherapy used to chelate redox-active metals and remove toxic metals from living systems
to avoid metal poisoning, is also discussed. |
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