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

Effects of H2O2, Fe2+ and Fe3+ on curcumin-induced chromosomal aberrations in CHO cells

The effects of H2O2, Fe2+ and Fe3+ on curcumin-induced clastogenicity were evaluated in CHO cells. Curcumin combined with H2O2 did not increase the chromosomal aberrations more than expected based on a simple additive effect. In contrast, the combination of curcumin-Fe significantly decreased the total number of chromosomal aberrations and the number of abnormal metaphases. The clastogenicity of curcumin may be related to its pro-oxidant properties and its ability to generate free radicals

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

Curcumin, a phenolic compound, possesses many pharmacological activities and is under clinical evaluation to treat different diseases. However, conflicting data about its stability have been reported. In this study, the kinetic degradation of curcumin from a natural curcuminoid mixture under various conditions (pH, temperature, and dielectric constant of the medium) was investigated. Moreover, the degradation of pure curcumin at some selected conditions was also determined. To fully solubilize curcumin and to prevent precipitation of curcumin that occurs when low concentrations of co–solvent are present, a 50:50 (v/v) aqueous buffer/methanol mixture was used as standard medium to study its degradation kinetics. The results showed that degradation of curcumin both as pure compound and present in the curcuminoid mixture followed first order kinetic reaction. It was further shown that an increasing pH, temperature, and dielectric constant of the medium resulted in an increase in the degradation rate. Curcumin showed rapid degradation due to autoxidation in aqueous buffer pH = 8.0 with a rate constant of 280 × 10-3h-1, corresponding with a half–life (t1/2) of 2.5 h. Dioxygenated bicyclopentadione was identified as the final degradation product. Importantly, curcumin loaded as curcuminoid mixture in ω–methoxy poly (ethylene glycol)–b–(N–(2–benzoyloxypropyl) methacrylamide) (mPEG–HPMA–Bz) polymeric micelles and in Triton X–100 micelles was about 300–500 times more stable than in aqueous buffer. Therefore, loading of curcumin into polymeric micelles is a promising approach to stabilize this compound and develop formulations suitable for further pharmaceutical and clinical studies