Roles of selenium in endotoxin-induced lipid peroxidation in the rats liver and in nitric oxide production in J774A.1 cells

Abstract

We examined the role of selenium (Se) in the mechanism of oxidative stress caused by endotoxin by feeding rats deficient a diet in this element. In rats fed the Se-deficient diet (concentration of Se, less than 0.027 μg g −1) for 10 weeks, Se level and glutathione peroxidase (GSH-Px) activity in the liver were about 47 and 43% lower, respectively, than those in rats fed a Se-adequate diet (Se, 0.2 μg g −1). Rat fed the Se-deficient diet and given endotoxin (6 mg kg −1, i.p.) showed a mortality rates of about 43% at 18 h. Nevertheless, no lethality was observed with endotoxin (4 mg kg −1, i.p.) challenge. Levels of serum lactate dehydrogenase and acid phosphatase leakage were significantly higher in Se-deficient rats than those in Se-adequate diet 18 h after endotoxin (4 mg kg −1, i.p.) challenge. Superoxide anion generation and lipid peroxide formation in the liver of Se-deficient rat were markedly increased 18 h after endotoxin (4 mg kg −1, i.p.) injection compared with those in the endotoxin/Se-adequate diet group, whereas non-protein sulfhydryl level in the liver after administration of endotoxin to Se-deficient rats was lower than that in Se-adequate rats treated with endotoxin. We investigated whether Se can suppress nitric oxide (NO) generation and cytotoxicity in endotoxin-treated J774A.1 cells. Treatment with Se (10 −6 M) markedly inhibited endotoxin (0.1 μg ml −1)-induced NO production in J774A.1 cells. Se induced an increased activity of GSH-Px in cells after 24 h of incubation, suggesting that the preventive effect of Se on NO production in endotoxemia is due to the induction of Se–GSH-Px activity. However, Se did not affect endotoxin-induced cytotoxicity in J774A.1 cells. These findings suggested that the oxidative stress caused by endotoxin may be due, at least in part, to changes in Se regulation during endotoxemia.