Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Transient postprandial ischemia is associated with increased intestinal fatty acid binding protein in patients with chronic gastrointestinal ischemia

Background Chronic gastrointestinal ischemia (CGI) is still a difficult diagnosis to make. Currently, the only diagnostic with an acceptable sensitivity for actual mucosal ischemia is gastrointestinal tonometry. However, tonometry is a cumbersome and invasive diagnostic test. We are in need of a more simple, noninvasive test for diagnosing mucosal ischemia. A sensitive and early serum marker could be of great use in this setting. The aim of this study was to evaluate the use of promising serum markers for mucosal ischemia [intestinal fatty acid binding protein (I-FABP), D-lactate, and lipopolysaccharide] and compared findings with corresponding gastrointestinal tonometry measurements. Methods Patients referred for evaluation of CGI were included. All patients had visualization of abdominal arteries and gastrointestinal tonometry. Before, during, and after tonometry blood samples were drawn for measurements of serum markers. Results Forty-nine patients were eligible for evaluation. CGI was diagnosed in 24 (49%) patients. The baseline measurements showed a significant increase in I-FABP before exercise tonometry in the abnormal-response groups compared with the normal-response group, respectively, 0.45 and 1.3 mu g/l (P=0.04). An abnormal response on meal tonometry was associated with increased I-FABP levels, 1, 2, and 4 h after tonometry, compared with the patients with a normal response, respectively, 1.26, 1.11, and 0.58 mu g/l (P=0.048, 0.01, and 0.03). The measurements of D-lactate and lipopolysaccharide were undetectable, or low, at all different points of time. Conclusion Transient postprandial mucosal ischemia, as detected with gastrointestinal tonometry, is associated with increased I-FABP levels, indicating epithelial damage. Late markers for mucosal ischemia remained negative. Eur J Gastroenterol Hepatol 21:278-282 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins