Role of Superoxide Radicals in Cytotoxic Effects of Fe-NTA on Cultured Normal Liver Epithelial Cells

We studied the cytotoxic effects of ferric nitrilotriacetate (Fe-NTA) on normal rat liver epithelial cells (RL34) cultured in medium containing 10 % fetal calf serum. Marked cytolysis was present in cells exposed to ?? 25 μg/ml iron of Fe-NTA, but not all the cells exposed to 50 μg/ml iron were lethally injured. The remaining cells showed anomalous growth, namely cell pile-up and aggregation.Superoxide dismutase inhibited this iron-induced cytotoxicity, whereas catalase, mannitol, dimethyl sulfoxide, and 1, 4-diazabicyclo-[2.2.2] octane did not. RL34 cells exposed to Fe-NTA actually produced a large amount of superoxide radicals (Oτ2), whereas unexposed control cells produced none. Allopurinol inhibited Oτ2 production and prevented cell injury by Fe-NTA. These results show that the injury to cells produced by Fe-NTA depends on the generation of Oτ2, the source of which may be xanthine oxidase.