Iron metabolism has been found to be significantly disturbed in type 2 diabetes and interferes with glucose metabolism (Lee et al., 2006b). Lowering iron pools generally improves insulin sensitivity. In addition, iron has been strongly implicated in nonalcoholic steatohepatitis, considered an early marker of insulin resistance (Machado and Cortez-Pinto, 2006). Elevated iron levels can predispose to coronary disease and myocardial infarction. Hypertension is believed to be a common risk factor of cardiovascular disease, related to metabolic syndrome and obesity, mediated

mainly by elevated levels of ROS in which iron plays a key role (LaMarca et al., 2008). Epacadostat Positive effects of iron depletion in women due to menstruation have

been associated with the lowering risk of cardiovascular-disease that disappears in post-menopause. Cardiovascular disease is a multifactorial disorder in which lipid metabolism, life style (smoking, stress), coronary artery disease and others play their concerted roles (Touyz and Schiffrin, 2004). It has been MK0683 ic50 communicated that iron mediated formation of superoxide radical and hydroxyl radical during development of heart disease, mainly during reperfusion injury, can be inhibited by iron chelators. Anemia is a potential risk factor and has been associated with heart failure (Mozaffarian et al., 2003 and Bolger et al., 2006), pointing to a role for dysregulation of iron metabolism. This points to the necessity of our understanding that exact speciation of iron in chronic anemias is linked to inflammatory diseases (Weiss and Goodnough, 2005). Atherosclerosis is an inflammatory condition accompanied by the accumulation of iron and oxidized lipids and fibrous elements in arteries as plaques. There is a correlation between iron status and atherosclerosis; free or poorly ligated iron can participate in lipid peroxidation

and protein peroxidation. The iron levels found in plagues correlated with the amount of oxidized proteins. Electron Paramagnetic Resonance (EPR) has been employed to demonstrate eltoprazine that atherosclerotic tissue contained 17 times more iron (EPR detectable ferric) than equivalent healthy tissue (Stadler et al., 2004). Transition metal ions have been implicated in etiology of neurodegenerative disorders (Bush, 2003). Dysregulation of brain iron (and also copper, see below) homeostasis is a key factor to early neuropathological events in Alzheimer’s disease (AD), including oxidative stress, inflammatory processes, amyloid β deposition, tau phosphorylation, and neuronal cell cycle regulatory failure, leading to apoptosis (Bush and Curtain, 2008).