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

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 ra ts fed the Se-deficient diet (concentration of Se, less than 0.027 mug g(-1 )) for 10 weeks, Se level and glutathione peroxidase (GSH-Px) activity in t he liver were about 47 and 43% lower, respectively, than those in rats fed a Se-adequate diet (Se, 0.2 mug g(-1)). Rat fed the Se-deficient diet and g iven 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 phosphatas e leakage were significantly higher in Se-deficient rats than those in Se-a dequate 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.) injec tion compared with those in the endotoxin;Se-adequate diet group. whereas n on-protein sulfhydryl level in the liver after administration of endotoxin to Se-deficient rats was lower than that in Se-adequate rats treated with e ndotoxin. We investigated whether Se can suppress nitric oxide (NO) generat ion and cytotoxicity in endotoxin-treated J774A.1 cells. Treatment with Se( 10(-6) M) markedly inhibited endotoxin (0.1 mug ml(-1))-induced NO producti on in J774A.1 cells. Se induced an increased activity of GSH-Px in cells af ter 24 h of incubation, suggesting that the preventive effect of Se on NO p roduction in endotoxemia is due to the induction of Se-GSH-Px activity. How ever, Se did not affect endotoxin-induced cytotoxicity in J774A.1 cells. Th ese findings suggested that the oxidative stress caused by endotoxin may be due, at least in part, to changes in Sr regulation during endotoxemia. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.