Role of Selenium‐Dependent Glutathione Peroxidase in Protecting against t‐Butyl Hydroperoxide‐Induced Damage in Hepatocytes

: 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.