Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes

Mechanisms of selenite cytotoxicity were examined using isolated rat hepatocytes. When selenite was added to a suspension of rat hepatocytes, intracellular reduced glutathione (GSH) was decreased and the oxygen consumption rate was increased. Subsequently, thiobarbituric acid-reactive substances (TBA-RS) and lactate dehydrogenase (LDH) leakage were increased. A ferric iron chelator, desferrioxamine (DF), and a synthetic superoxide dismutase (SOD) mimic, desferrioxamine manganese (DFMn), reduced the selenite toxicity. These results suggest that superoxide anion and its reactive metabolites such as the hydroxyl radical may be involved in the cytotoxicity of selenite.