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

Ramification of the a. mesenterica cranialis and its variability in the guinea pig (Cavia aperea f. porcellus).

The authors studied ramification of the a. mesenterica cranialis and its variability in 30 guinea pigs (Cavia aperea f. porcellus) after injecting red-dyed latex into their arterial bed. In every case, this artery arose from the truncus hepato-mesentericus, which in turn was a branch of a thick arterial truncus coeliaco-mesentericus. After leaving its site of origin, the a. mesenterica cranialis formed a long arc whose convexity was directed leftwards and caudally. Its first branch was most frequently (18 cases-60%) the a. colica media. In seven cases (23.3%) this artery arose together with the a. pancreaticoduodenalis caudalis from the same site. The a. pancreaticoduodenalis caudalis was the first branch of the a. mesenterica cranialis in two cases only (6.7%). In 18 cases (69%) the a. pancreaticoduodenalis caudalis was the second branch of the a. mesenterica cranialis and in seven cases (23.3%) it arose from the same site as the a. colica media. It supplied the caudal part of the pancreas and the duodenum as far as the flexura duodenojejunalis, where it formed an anastomosis with the first a. jejunalis. In every case, the ileum, caecum and colon were supplied by a thick a. ileocaecocolica, which after giving off the last a. jejunalis, formed a continuation of the trunk of the a. mesenterica cranialis. Near the ileocaecal junction it divided into a r. ileacus, rr. caecales, a r. prae--and retrocaecalis and a r. colicus. The caecum was further fed by thick r1. caecales which usually branched from the middle segment of the a. mesenterica cranialis.(ABSTRACT TRUNCATED AT 250 WORDS

Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death via activation of calpains

10.1096/fj.03-1096fjeFASEB Journal18121395-1397FAJO