Increased thromboxane A2 synthesis by rat lung neutrophils during selenium deficiency

Abstract Modulation of cellular hydroperoxide levels is considered one of the important physiological mechanisms for regulating the synthesis of prostaglandins (PGs) and leukotrienes (LTs) in mammalian cells. Both vitamin E and selenium (Se) have the potential to affect the concentration of peroxides and, thus, the biosynthesis of eicosanoids. To gain insight into some of the molecular mechanisms underlying the regulation of the arachidonic acid cascade by vitamin E and Se, we have investigated the influence of altered vitamin E and Se nutrition on the ability of polymorphonuclear leukocytes (PMNs) derived from endotoxin-challenged lung to secrete arachidonic acid metabolites. Selenium deficiency had no significant effect (p>0.05) on lavage fluid levels of thromboxane (TX) B 2 , LTB 4 or LTC 4 . Vitamin E deficiency, however, led to a significant increase in LTB 4 recovered from lavage fluid while having no effect on TXB 2 . In contrast, Se deficiency, although producing no discernible effects on the production of LTB 4 , resulted in a significant increase in the release of TXB 2 by PMNs. An increase in TXB 2 release was seen in both in vitro -stimulated and nonstimulated PMNs. Vitamin E deficiency appeared to induce an enhancement of LTB 4 release by PMNs but the increase was not statistically significant. No detectable levels of LTC 4 were found in PMN cultures stimulated with either zymosan or A23187. Thus, these studies indicate that deficiencies of either Se or vitamin E lead to alterations in the metabolism of arachidonic acid in the lung.