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 greater than or equal to 25 micrograms/ml iron of Fe-NTA, but not all the cells exposed to 50 micrograms/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 (O2-.), whereas unexposed control cells produced none. Allopurinol inhibited O2-. 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 O2-., the source of which may be xanthine oxidase.
Yamada
M
M
Department of Pathology, Okayama University Medical School, Japan.
Okigaki
T
T
Awai
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives*; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
D005290:Ferric Compounds; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate