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

Effect of low dose, short-term creatine supplementation on muscle power output in elite youth soccer players

Background To determine the effects of a low dose, short-term Creatine monohydrate (Cr) supplementation (0.03 g.kg.d−1 during 14 d) on muscle power output in elite youth soccer players. Methods Using a two-group matched, double blind, placebo-controlled design, nineteen male soccer players (mean age = 17.0 ± 0.5 years) were randomly assigned to either Cr (N = 9) or placebo (N = 10) group. Before and after supplementation, participants performed a 30s Wingate Anaerobic Test (WAnT) to assess peak power output (PPO), mean power output (MPO), fatigue index (FI), and total work. Results There were significant increases in both PPO and MPO after the Cr supplementation period (P ≤ 0.05) but not the placebo period. There were also significant increases in total work, but not FI, after the Cr supplementation and placebo periods (P ≤ 0.05). Notably, there were differences in total work between the Cr and placebo groups after (P ≤ 0.05) but not before the 14 d supplementation period. Conclusion There is substantial evidence to indicate that a low-dose, short-term oral Cr supplementation beneficially affected muscle power output in elite youth soccer players

Delphinidin activates NFAT and induces IL-2 production through SOCE in T cells

Delphinidin is an anthocyanidin that possesses antioxidant and anti-inflammatory effects; however, some reports suggest that delphinidin has pro-inflammatory properties. For this reason, we assessed the effect of delphinidin on cytokine production in T cells. We demonstrated that delphinidin increased the cytosolic-free Ca2+ concentration by releasing Ca2+ from intracellular stores and increasing Ca2+ entry. The putative Ca2+ release activated Ca2+ (CRAC) channel inhibitors BTP2 and gadolinium reduced the calcium entry stimulated by the anthocyanidin. Delphinidin induced nuclear factor of activated T cells (NFAT) translocation and NFAT-Luc activity in Jurkat cells and was dependent on the CRAC channel and calcineurin pathway. Delphinidin increased the mRNA expression and production of IL-2 in Jurkat cells and was inhibited by BTP2 and cyclosporine A. Using peripheral blood lymphocytes, we demonstrated that delphinidin increased the production of IL-2 and IFN-¿ and was inhibited by BTP2. Taken together, our results suggest that delphinidin exerts immunostimulatory effects on T cells by increasing cytokine production through CRAC channel and NFAT activation. © 2013 Springer Science+Business Media New York.This work was supported by Grants from Consorcio de Tecnología e Innovación para la Salud CTI-Salud (CTE-06), Chile (CONICYT 21090900 and CONICYT T-24100037).Peer Reviewe