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

• Published in: Toxicology letters Vol. 118; no. 1; pp. 69 - 77
• Main Authors: Sakaguchi, Shuhei, Iizuka, Yukisumi, Furusawa, Shinobu, Tanaka, Yorihisa, Takayanagi, Motoaki, Takayanagi, Yoshio
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 20.12.2000; Amsterdam Elsevier Science
• Subjects: Animals; Bacterial Toxins - toxicity; Bacteriology; Biological and medical sciences; Cell Line; Cytotoxicity; Electrophoresis; Endotoxin; Endotoxins - toxicity; Fundamental and applied biological sciences. Psychology; Glutathione Peroxidase - metabolism; Isoenzymes - blood; L-Lactate Dehydrogenase - blood; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; Lipid Peroxides - biosynthesis; Liver - drug effects; Liver - enzymology; Liver - metabolism; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Microbiology; Nitric oxide; Nitric Oxide - biosynthesis; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Rats; Rats, Wistar; Selenium; Selenium - metabolism; Selenium - pharmacology; Selenium - physiology; Sulfhydryl Compounds - metabolism; Superoxides - metabolism; Lipid peroxidation; Cytotoxicity; Selenium; Endotoxin; Nitric oxide; Oxidative stress; Intraperitoneal administration; Deficient diet; Monocyte; Rat; Toxicity; Liver; Mortality; Rodentia; Lipids; Trace element; Vertebrata; Mammalia; Cell line; Mouse; Animal; Lipopolysaccharide; Mechanism of action; Peroxidation
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(00)00263-0

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.