, 2002 and Matés et al., 2008). Redox active metals may undergo cycling reactions participating in the transfer of electrons between metals and substrates and therefore may play an important role in the maintenance of redox homeostasis, a phenomenon tightly linked with metal homeostasis (Lindeque et al., 2010). Disruption of metal homeostasis may lead uncontrolled metal-mediated formation

of deleterious free radicals participating in the modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulphydryl homeostasis (Gutteridge, 1995 and Valko et al., 2007). Humans may be exposed to redox-inert elements such as cadmium and arsenic which have no known biological Navitoclax ic50 function and are even known to be toxic at low concentrations. In contaminated areas, exposure to these elements arises from a variety of natural sources, including air, drinking water Selleck Talazoparib and food. While redox active metals undergo redox-cycling reactions, for the group of redox-inert elements, the primary route for their toxicity and carcinogenicity is depletion of glutathione, bonding to sulphydryl groups of proteins and other mechansisms of action (Speisky et al., 2008, Sinicropi et al., 2010 and Peralta-Videa et al., 2009). All these aspects of metals acting in biological systems

Adenosine triphosphate make the purpose of this paper to provide an overview of the current state of knowledge of the following: the role of redox-active metals, namely iron, copper, chromium, cobalt and redox-inert metals cadmium and arsenic in the formation of reactive oxygen and nitrogen species and their involvement in the development of human disease and ageing.

A special attention is paid to the anti-inflammatory role of the redox-inert metal zinc. Iron occurs in the oxidation states +II and +III. The ferrous ions are soluble in biological fluids and generate in the presence of oxygen damaging hydroxyl radicals. The ferrous ions are unstable in aqueous media and tend to react with molecular oxygen to form ferric ions and superoxide anion radical. The oxidized form of iron is insoluble in water at neutral pH and precipitates in the form of ferric hydroxide (Jones-Lee and Lee, 2005). Paradoxically, despite the fact that both iron ions, ferrous and ferric are so inaccessible, iron is the key catalytic site of many of the enzymes and oxygen-transporting proteins in cells. Although iron is vital for life, it can be toxic when it is present in excess (Lee et al., 2006a). Iron homeostasis is a complex process, as there are many different proteins that respond not only to the total body burden of iron, but also to stimuli such as hypoxia, anemia and inflammation.