Okada S, Hamazaki S, Ebina Y, Li J L, Midorikawa O
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
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.
次氮基三乙酸的铁和铝络合物会在Wistar大鼠中引起严重的肾毒性。此外，在接受次氮基三乙酸铁治疗的动物中，肾细胞癌的发病率很高。进行本研究是为了观察脂质过氧化是否与次氮基三乙酸铁的毒性有关。次氮基三乙酸铁比任何铁盐都有更多可被博来霉素检测到的“游离”铁，而与去铁胺或硫酸软骨素铁络合的铁则没有。在维生素E缺乏的大鼠中，次氮基三乙酸铁在体内的毒性更为明显。与维生素E充足或补充了维生素E的大鼠相比，维生素E缺乏的大鼠肾脏中存在大量明显升高的硫代巴比妥酸反应性物质。在给药第58天前死亡的维生素E充足的大鼠中，未络合的次氮基三乙酸或次氮基三乙酸铝不会产生任何硫代巴比妥酸反应性物质。我们认为，铁刺激自由基产生导致脂质过氧化是次氮基三乙酸铁介导的肾毒性的主要原因。维生素E作为一种已知的自由基清除剂，能有效预防这种铁诱导的毒性。
