Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation

Biochim Biophys Acta. 1987 Oct 31;922(1):28-33. doi: 10.1016/0005-2760(87)90241-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ferric Compounds / antagonists & inhibitors
  • Ferric Compounds / toxicity*
  • Free Radicals
  • Iron / analysis
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control
  • Lipid Peroxides / biosynthesis*
  • Male
  • Nitrilotriacetic Acid* / analogs & derivatives*
  • Rats
  • Rats, Inbred Strains
  • Time Factors
  • Vitamin E / pharmacology*
  • Vitamin E Deficiency / metabolism


  • Ferric Compounds
  • Free Radicals
  • Lipid Peroxides
  • Vitamin E
  • Iron
  • Nitrilotriacetic Acid
  • ferric nitrilotriacetate