title: 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 microg 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 microg 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 microg 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.
authors.affiliation: First Department of Hygienic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Iizuka
authors.forename: S
authors.initials: S
authors.lastname: Furusawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Y
authors.initials: Y
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D004586:Electrophoresis; D004731:Endotoxins / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007527:Isoenzymes / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004731:Endotoxins; D007527:Isoenzymes; D008054:Lipid Peroxides; D013438:Sulfhydryl Compounds; C027952:salmonella toxin; D013481:Superoxides; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D012643:Selenium