Uptake of iron and nitrilotriacetate (NTA) in rat liver and the toxic effect of Fe-NTA.
A previous study has shown that a single injection of ferric nitrilotriacetate (Fe-NTA) produces hepatic parenchymal iron loading in rats. The present paper reports on iron uptake by rat liver and iron toxicity in the liver after a single injection of Fe-NTA (7.5 mg Fe/kg B.W.). Iron uptake was examined with 59Fe-NTA and Fe-[14C]-NTA. Thirty percent of the injected 59Fe was incorporated in the liver non-heme iron fraction at 3 h and retained for 240 h. Only 1% of the 14C injected as Fe-[14C]-NTA was taken up by the liver at 3 h. Gel filtration with a Sephadex G-25 column of the supernatant fraction of the liver obtained 3 h after the injection showed two peaks of 14C activity. One was eluted in the void volume, and the other corresponded to [14C]-NTA. The former had a molecular weight of 5,000-10,000 as determined with a Sephacryl S-300 column and also had 59Fe activity. The electron spin resonance spectra showed that the generation of a free radical in the liver was initiated within 1 h of the iron administration. The free radical generated in the serum by Fe-NTA was revealed to be superoxide by the spin trapping method. These results suggest that Fe-NTA transfers iron to transferrin in the serum and induces hepatic iron loading. Small amounts of the injected iron were taken up by the liver as Fe-NTA and generated superoxide which may have induced lipid peroxidation of the cellular membranes.
D000085:Acetates / Q000378:metabolism*; D000818:Animals; D005290:Ferric Compounds / Q000494:pharmacology*; D005293:Ferritins / Q000378:metabolism; D005609:Free Radicals; D006485:Hemosiderin / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009571:Nitrilotriacetic Acid / Q000378:metabolism* / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D000085:Acetates; D005290:Ferric Compounds; D005609:Free Radicals; D013481:Superoxides; D005293:Ferritins; D006485:Hemosiderin; D007501:Iron; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate