Impact of selenium supplementation on fish antiviral responses: a whole transcriptomic analysis in rainbow trout (Oncorhynchus mykiss) fed supranutritional levels of Sel-Plex®

The superoxide free radical has come to occupy an amazingly central role in a wide variety of diseases. Our metabolic focus on aerobic energy metabolism in all cell types, coupled with some chemical peculiarities of the oxygen molecule itself, contribute to the phenomenon. Superoxide is not, as we once thought, just a toxic but unavoidable byproduct of oxygen metabolism. Rather it appears to be a carefully regulated metabolite capable of signaling and communicating important information to the cell's genetic machinery. Redox regulation of gene expression by superoxide and other related oxidants and antioxidants is beginning to unfold as a vital mechanism in health and disease.

Following the publication of the landmark trial of Clark et al. in 1996 that appeared to show that Se could reduce the risk of cancer, awareness of the importance of Se to human health has markedly increased. As a result, there is now much more aggressive marketing of Se supplements and functional foods, even in situations where additional consumption of Se is inappropriate. The present review addresses how Se gets into the food chain, the wide variability in Se content of foods and the very different levels of intake between countries and regions. Though it is clear that there are adverse consequences for health of both deficient and excessive intake, health effects at intermediate levels of intake are less certain. Thus it is difficult to define optimal intake which depends on a large number of factors, such as which functions of Se are most relevant to a particular disease state, which species of Se is most prominent in the Se source, which health condition is being considered, the adequacy or otherwise of intake of other nutrients, the presence of additional stressors, and lastly whether the ability to make selenoproteins may be compromised. These complexities need to be understood, particularly by policy makers, in order to make informed judgments. Potential solutions for increasing Se intake, where required, include agronomic biofortification and genetic biofortification or, for individuals, increased intake of naturally Se-rich foods, functional foods or supplements. The difficulties of balancing the risks and benefits in relation to Se intake are highlighted.

Phagocytes such as neutrophils and macrophages produce reactive oxygen species (ROS) during phagocytosis or stimulation with a wide variety of agents through activation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase that is assembled at the plasma membrane from resident plasma membrane and cytosolic protein components. One of the subunits of the phagocyte NADPH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes. Physiologic generation of ROS has been implicated in a variety of physiologic responses from transcriptional activation to cell proliferation and apoptosis. The increase in superoxide and hydrogen peroxide (H2O2) that results from stimulation of the NADPH oxidase is transient, in part due to the presence of the antioxidant enzymes, which return their concentrations to the prestimulation steady state level. Thus, the antioxidant enzymes may function in the "turn-off" phase of signal transduction by ROS. During its transient elevation, H2O2 may act as a modifier of key signaling enzymes through reversible oxidation of critical thiols. The rapid reaction of thiols with H2O2 when in their unprotonated state would provide a potential mechanism for the specificity that is necessary for physiologic cell signaling.