Catalytic oxidant scavenging by selenium-containing compounds: Reduction of selenoxides and N-chloramines by thiols and redox enzymes

Abstract

Myeloperoxidase produces strong oxidants during the immune response to destroy invading pathogens. However, these oxidants can also cause tissue damage, which contributes to the development of numerous inflammatory diseases. Selenium containing compounds, including selenomethionine (SeMet) and 1,4-anhydro-5-seleno-D-talitol (SeTal), react rapidly with different MPO-derived oxidants to form the respective selenoxides (SeMetO and SeTalO). This study investigates the susceptibility of these selenoxides to undergo reduction back to the parent compounds by intracellular reducing systems, including glutathione (GSH) and the glutathione reductase and thioredoxin reductase systems. GSH is shown to reduce SeMetO and SeTalO, with consequent formation of GSSG with apparent second order rate constants, k2, in the range 103–104 M−1 s−1. Glutathione reductase reduces both SeMetO and SeTalO at the expense of NADPH via formation of GSSG, whereas thioredoxin reductase acts only on SeMetO. The presence of SeMet and SeTal also increased the rate at which NADPH was consumed by the glutathione reductase system in the presence of N-chloramines. In contrast, the presence of SeMet and SeTal reduced the rate of NADPH consumption by the thioredoxin reductase system after addition of N-chloramines, consistent with the rapid formation of selenoxides, but only slow reduction by thioredoxin reductase. These results support a potential role of seleno compounds to act as catalytic scavengers of MPO-derived oxidants, particularly in the presence of glutathione reductase and NADPH, assuming that sufficient plasma levels of the parent selenoether can be achieved in vivo following supplementation.

The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease

“…One potential species is taurine, which is present in high concentrations within neutrophils (152), with supplementation with taurine shown to decrease macrophage infiltration, elastin fragmentation, and MMP activation associated with the overexpression of MPO in an in vivo model of abdominal aortic aneurysms (128). Similarly, some seleniumcontaining compounds can react rapidly with MPO-derived oxidants (36), with the resulting selenoxides able to be catalytically recycled by cellular reductants and antioxidant enzymes (37). Although there are positive associations with selenium supplementation and beneficial disease outcomes, further studies are required to specifically assess whether this is related to a reduction in MPO-induced damage (35).…”

Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

“…Selenium species offer a promising, alternative therapy against oxidative stress within the setting of CVD due to their ability to rapidly react with a variety of biologically-relevant oxidants [16,17,18], including H 2 O 2 and HOCl, at rates comparable to the reaction of these oxidants with primary cellular targets such as abundant low molecular-weight and protein thiols (R-SH) species [19], whilst also promoting the activity of endogenous seleno-dependent antioxidants, particularly those of the GPx and Trxrd systems [20,21,22,23,24,25,26]. In addition, recent studies highlight a potential catalytic role for selenium-containing compounds, including selenomethionine (SeMet) to scavenge oxidants [27,28].…”

“…Once present and incorporated, SeMet is able to react with oxidants and then be catalytically recycled back to an active form by low molecular environmental reductants and intracellular reducing systems [50,51] including glutathione reductase (GR) and Trxrd. In this respect, the antioxidant capacity of SeMet is continually regenerated at the cellular level [27,28,51]. Given this, the aims of the current study were to evaluate the potentially protective role of SeMet supplementation in modulating the extent of cellular damage observed in an in vitro cardiomyocyte model exposed to HOCl and an experimental in vivo model of cardiac I/R injury.…”

Targeting the vascular dysfunction: Potential treatments for preeclampsia

“…Furthermore, selenium may not be any more beneficial at combating the oxidative stress of preeclampsia than any other antioxidant. However, recently a water‐soluble selenium‐containing sugar (1,4‐anhydro‐4‐seleno‐D‐talitol; SeTal) that is a potent antioxidant was demonstrated to accelerate wound closure in diabetic mice by improving vascular perfusion at the wound site (J. C. Kwan et al, 2016 unpublished data ). Furthermore, SeTal, but not selenium, prevents the onset of vascular dysfunction in isolated mouse aorta under conditions of acute oxidative stress by decreasing superoxide levels and increasing basal NO availability .…”