Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and...

Lipopolysaccharide (LPS) produces reactive oxygen species (ROS) and nitric oxide (NO) in macrophages. These molecules are involved in inflammation associated with endotoxic shock. Selenium (Se), a biologically essential trace element, modulates the functions of many regulatory proteins involved in signal transduction and affects a variety of cellular activities, including cell growth and survival. We demonstrate that Se attenuated LPS-induced ROS and NO production in murine macrophage cultures in vitro. This Se-decreased production of NO was demonstrated by decreases in both mRNA and protein expression for inducible NO synthase (iNOS). The preventive effects of Se on iNOS were p38 mitogen-activated protein kinase- and nuclear factor-kappaB-dependent. Se specifically blocked the LPS-induced activation of p38 but not that of c-jun-N-terminal kinase and extracellular signal-regulated kinase; the p38-specific pathway was confirmed using p38 inhibitor SB 203580. These results suggest that the mechanism by which Se may act as an anti-inflammatory agent and that Se may be considered as a possible preventive intervention for endotoxemia, particularly in Se-deficient locations. However, the efficacy and safety of Se need to be further investigated, because long-term intake > 0.4 mg Se/day in adults can produce adverse effects.