Interaction kinetics of selenium-containing compounds with oxidants.

Selenium compounds have been identified as potential oxidant scavengers for biological applications due to the nucleophilicity of Se, and the ease of oxidation of the selenium centre. Previous studies have reported apparent second order rate constants for a number of oxidants (e.g. HOCl, ONOOH) with some selenium species, but these data are limited. Here we provide apparent second order rate constants for reaction of selenols (RSeH), selenides (RSeR') and diselenides (RSeSeR') with biologically-relevant oxidants (HOCl, H2O2, other peroxides) as well as overall consumption data for the excited state species singlet oxygen (1O2). Selenols show very high reactivity with HOCl and 1O2, with rate constants > 108 M-1 s-1, whilst selenides and diselenides typically react with rate constants one- (selenides) or two- (diselenides) orders of magnitude slower. Rate constants for reaction of diselenides with H2O2 and other hydroperoxides are much slower, with k for H2O2 being <1 M-1 s-1, and for amino acid and peptide hydroperoxides ~102 M-1 s-1. The rate constants determined for HOCl and 1O2 with these selenium species are greater than, or similar to, rate constants for amino acid side chains on proteins, including the corresponding sulfur-centered species (Cys and Met), suggesting that selenium containing compounds may be effective oxidant scavengers. Some of these reactions may be catalytic in nature due to ready recycling of the oxidized selenium species. These data may aid the development of highly efficacious, and catalytic, oxidant scavengers.

Iodide modulates protein damage induced by the inflammation-associated heme enzyme myeloperoxidase.

Iodide ions (I-) are an essential dietary mineral, and crucial for mental and physical development, fertility and thyroid function. I- is also a high affinity substrate for the heme enzyme myeloperoxidase (MPO), which is involved in bacterial cell killing during the immune response, and also host tissue damage during inflammation. In the presence of H2O2 and Cl-, MPO generates the powerful oxidant hypochlorous acid (HOCl), with excessive formation of this species linked to multiple inflammatory diseases. In this study, we have examined the hypothesis that elevated levels of I- would decrease HOCl formation and thereby protein damage induced by a MPO/Cl-/H2O2 system, by acting as a competitive substrate. The presence of increasing I- concentrations (0.1-10 µM; i.e. within the range readily achievable by oral supplementation in humans), decreased damage to both model proteins and extracellular matrix components as assessed by gross structural changes (SDS-PAGE), antibody recognition of parent and modified protein epitopes (ELISA), and quantification of both parent amino acid loss (UPLC) and formation of the HOCl-biomarker 3-chlorotyrosine (LC-MS) (reduced by ca. 50% at 10 µM I-). Elevated levels of I- ( > 1 µM) also protected against functional changes as assessed by a decreased loss of adhesion (eg. 40% vs. < 22% with >1 µM I-) of primary human coronary artery endothelial cells (HCAECs), to MPO-modified human plasma fibronectin. These data indicate that low micromolar concentrations of I-, which can be readily achieved in humans and are readily tolerated, may afford protection against cell and tissue damage induced by MPO.