Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation.
Iron and aluminum complexes of nitrilotriacetic acid cause severe nephrotoxicity in Wistar rats. In addition, a high incidence of renal cell carcinoma is seen in ferric nitrilotriacetate-treated animals. The present study was performed to see if lipid peroxidation is involved in ferric nitrilotriacetate toxicity. Ferric nitrilotriacetate had more bleomycin-detectable 'free' iron than any ferric salt, while iron complexed with desferrioxamine or ferric chondroitin sulfate had none. The toxicity of ferric nitrilotriacetate in vivo was more pronounced in vitamin E-deficient rats. A thiobarbituric acid-reactive substance was present in the kidneys of vitamin E-deficient rats in amounts markedly elevated compared to vitamin E-sufficient, or vitamin E-supplemented rats. Non-complexed nitrilotriacetate or aluminum nitrilotriacetate did not produce any thiobarbituric acid-reactive substance in vitamin E-sufficient rats died by the 58th day of administration. We suggest that the iron-stimulated production of free radicals leading to lipid peroxidation is the major cause of ferric nitrilotriacetate-mediated renal toxicity. Vitamin E, a known scavenger of free radicals, is effective in protecting against this iron-induced toxicity.
Okada
S
S
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Hamazaki
S
S
Ebina
Y
Y
Li
J L
JL
Midorikawa
O
O
D000818:Animals; D005290:Ferric Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005609:Free Radicals; D007501:Iron / Q000032:analysis; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism
D005290:Ferric Compounds; D005609:Free Radicals; D008054:Lipid Peroxides; D014810:Vitamin E; D007501:Iron; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate