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

Abstract

Oxidative renal tubular injuries and carcinogenesis induced by Fe(III)-nitrilotriacetate (NTA) and Fe(III)-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 Fe(III)-iminodiacetate (IDA), a novel iron-chelator, induced acute tubular injuries and lipid peroxidation to the same extent. We also prepared Fe(III)-IDA solutions at different pHs, and studied resultant oxidative injuries and physicochemical properties. The use of Fe(III)-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 Fe(III)-IDA had the same dimer structure from pH 6.2 to 7.2 as Fe(III)-NTA; but at a higher pH, iron polymerized and formed clusters. Fe(III)-IDA was crystallized, and this was confirmed by X-ray analysis and magnetic susceptibility measurements. These data indicated that Fe(III)-IDA possessed a linear mu-oxo bridged dinuclear iron (III) around neutral pH.

• Authors: Ryuichiro Mizuno, Teruyuki Kawabata, Yuichi Sutoh, Yuzo Nishida, Shigeru Okada
• Journal: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine (Biometals) Vol. 19 Issue 6 Pg. 675-83 (Dec 2006) ISSN: 0966-0844 [Print] Netherlands
• PMID: 16670936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Ferric Compounds
• Imino Acids
• Iron Chelating Agents
• Thiobarbituric Acid Reactive Substances
• Deoxyribose
• EDDA
• Edetic Acid
• Nitrilotriacetic Acid
• iminodiacetic acid
• ferric nitrilotriacetate

Topics

• Animals
• Carcinogens (toxicity)
• Deoxyribose (metabolism)
• Edetic Acid (analogs & derivatives, toxicity)
• Electron Spin Resonance Spectroscopy
• Ferric Compounds (toxicity)
• Hydrogen-Ion Concentration
• Imino Acids (toxicity)
• In Situ Nick-End Labeling
• Iron Chelating Agents (toxicity)
• Kidney Diseases (chemically induced)
• Kidney Tubules (drug effects, pathology)
• Male
• Nitrilotriacetic Acid (analogs & derivatives, toxicity)
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Spectrophotometry, Ultraviolet
• Thiobarbituric Acid Reactive Substances (analysis)