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

Adherence and side effects of three ferrous sulfate treatment regimens on anemic pregnant women in clinical trials Adesão e efeitos colaterais em ensaio clínico comparando três esquemas de tratamento com sulfato ferroso em gestantes anêmicas

The objective of this study was to analyze adherence and side effects of three iron supplement regimens (ferrous sulfate) on anemic pregnant women. The clinical trial involved 150 women between the 16th and 20th gestational weeks, at low obstetric risk and with hemoglobin concentration of between 8.0 and 11.0g/dL. Treatment was provided by ferrous sulfate with 60mg of elemental iron during 16 (± 1) weeks, in three regimens: single tablet a week (n = 48); single tablet twice a week (n = 53) or single tablet a day (n = 49). The outcomes were adherence, assessed through interviews and by counting tablets, and side effects, according to patient information. The adherence showed a declining trend (92%, 83% and 71%; p = 0.010) and the side effects revealed a growing trend (40%, 45% and 71%; p = 0.002) as the dosage increased. Diarrhea and epigastric pain were significantly associated with the dose administered (p = 0.002). These results suggest that in anemic pregnant women, complaints are directly proportional and the compliance is inversely proportional to the amount of medicinal iron.<br>O objetivo deste estudo foi analisar a adesão e os efeitos colaterais de três esquemas de suplementação com sulfato ferroso em gestantes anêmicas. O ensaio clínico incluiu 150 mulheres entre a 16ª e 20ª semanas de gestação, de baixo risco obstétrico e com concentração de hemoglobina entre 8,0 e 11,0g/dL. A intervenção foi realizada com 60mg de ferro elementar, durante 16 (±1) semanas, em três esquemas: uma drágea semanal (n = 48); uma drágea duas vezes por semana (n = 53) ou uma drágea diariamente (n = 49). Os desfechos foram adesão, verificada por entrevista e contagem das drágeas, e efeitos colaterais auto-relatados pelas pacientes. A adesão apresentou tendência declinante (92%, 83% e 71%; p = 0,010) e os efeitos colaterais, ascendente (40%, 45% e 71%; p = 0,002) com o aumento da dose prescrita. Diarréia e dor epigástrica estiveram significativamente associadas à dose administrada (p = 0,002). Os resultados sugerem que em gestantes anêmicas as queixas e a adesão ao tratamento com sulfato ferroso são, respectivamente, direta e inversamente proporcionais à quantidade do ferro medicamentoso