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Oxidative renal tubular injuries induced by aminocarboxylate-type iron (III) coordination compounds as candidate renal carcinogens

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Abstract

Oxidative renal tubular injuries and carcinogenesis induced by FeIII-nitrilotriacetate (NTA) and FeIII–ethylenediamine-N,N′-diacetate (EDDA) have been reported in rodent kidneys, but the identity of iron coordination structure essential for renal carcinogenesis, remains to be clarified. We compared renal tubular injuries caused by various low molecular weight aminocarboxylate type chelators with injuries due to NTA and EDDA. We found that FeIII-iminodiacetate (IDA), a novel iron-chelator, induced acute tubular injuries and lipid peroxidation to the same extent. We also prepared FeIII-IDA solutions at different pHs, and studied resultant oxidative injuries and physicochemical properties. The use of FeIII-IDA at pH 5.2, 6.2, and 7.2 resulted in renal tubular necrosis and apoptotic cell death, but neither tubular necrosis nor apoptosis was observed at pH 8.2. Spectrophotometric data suggested that FeIII-IDA had the same dimer structure from pH 6.2 to 7.2 as FeIII-NTA; but at a higher pH, iron polymerized and formed clusters. FeIII-IDA was crystallized, and this was confirmed by X-ray analysis and magnetic susceptibility measurements. These data indicated that FeIII-IDA possessed a linear μ-oxo bridged dinuclear iron (III) around neutral pH.

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Abbreviations

TUNEL:

TdT-mediated dUTP nick end labeling

TBARS:

thiobarbituric acid reactive substance

ESR:

electron spin resonance

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Acknowledegments

We are very grateful to Prof. S. Yamazaki (Department of Fundamental Science, Okayama University of Science) for his helpful discussion, and Prof. T. Tokii (Department of Physical and Inorganic Chemistry, Saga University) for measuring magnetic susceptibility.

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Authors and Affiliations

  1. Department of Pathological Research, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Ryuichiro Mizuno & Shigeru Okada

  2. Department of Applied Physics, Faculty of Science, Okayama University of Science, Okayama, Japan

    Teruyuki Kawabata

  3. Chemical Institute for Neurodegeneration (CIN), Faculty of Science, Yamagata University, Yamagata, Japan

    Yuichi Sutoh & Yuzo Nishida

Authors
  1. Ryuichiro Mizuno
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  2. Teruyuki Kawabata
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  3. Yuichi Sutoh
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  4. Yuzo Nishida
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  5. Shigeru Okada
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Correspondence to Ryuichiro Mizuno.

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Mizuno, R., Kawabata, T., Sutoh, Y. et al. Oxidative renal tubular injuries induced by aminocarboxylate-type iron (III) coordination compounds as candidate renal carcinogens. Biometals 19, 675–683 (2006). https://doi.org/10.1007/s10534-006-9004-4

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  • DOI: https://doi.org/10.1007/s10534-006-9004-4

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