title: Role of selenium-dependent glutathione peroxidase in protecting against t-butyl hydroperoxide-induced damage in hepatocytes.
abstract: The role of the selenoenzyme glutathione peroxidase (Se-GSHPx) in protecting against oxidative injury was studied in hepatocytes isolated from rats fed either a low-selenium (Se-) or a selenium-adequate (Se+, control) diet. In rats fed Se- diet for eight weeks the selenium content of plasma and liver was lowered to 15 and 8%, respectively. No Se-GSHPx and only 5% of total GSHPx activity was detected in Se- hepatocytes. However, the Se- hepatocytes were as resistant as the Se+ cells to oxidative injury by 0.8 mM tert-butyl hydroperoxide (t-BuOOH), or 0.2 mM t-BuOOH plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of oxidized glutathione (GSSG) reductase. Only at 1.5 mM t-BuOOH or at 0.5 mM t-BuOOH with BCNU were cell damage and lipid peroxidation more evident in Se- cells. At all t-BuOOH concentrations used the depletion of cellular glutathione (GSH) was similar in magnitude in Se- and Se+ cells, but Se+ cells released more glutathione (mainly GSSG), obviously due to their higher Se-GSHPx activity. These results suggest that hepatocytes devoid of Se-GSHPx activity maintain a high capacity to resist peroxidative attack, either via residual (non-Se)GSHPx activity or other compensatory GSH-associated detoxication mechanisms.
authors.affiliation: Research Laboratories, Alko Ltd., Helsinki, Finland.
authors.forename: C
authors.initials: C
authors.lastname: Yuan
authors.forename: K E
authors.initials: KE
authors.lastname: Penttilä
authors.forename: G
authors.initials: G
authors.lastname: Alfthan
authors.forename: K O
authors.initials: KO
authors.lastname: Lindros
mesh_terms: D000818:Animals; D005979:Glutathione Peroxidase / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D012643:Selenium / Q000172:deficiency / Q000502:physiology*; D020122:tert-Butylhydroperoxide
chemical_list: D010545:Peroxides; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D012643:Selenium