ESR characterization and metallokinetic analysis of Cr(V) in the blood of rats given carcinogen chromate(VI) compounds.
It has been shown that bio-trace metal elements are related to many diseases and the aging process. For many years, carcinogen hexavalent chromium (VI) has been known to be toxic to animals, but its dynamic toxicological mechanism is not sufficiently elucidated. Bioinorganic chemistry in terms of metallokinetic analysis of beneficial or toxic metal ions and their complexes is an important investigation for understanding their biochemical and physiological roles. We have tried to examine the real-time behavior of paramagnetic metal ions and complexes in animals, in which electron spin resonance (ESR) was capable of measuring paramagnetic species in chemical and biological systems. On the basis of our previous results on stable nitroxide spin probes, we have developed the in vivo blood circulation monitoring-electron spin resonance (BCM-ESR) method to analyze time-dependent ESR signal changes due to paramagnetic metal ions and their complexes in real time. When K2Cr2O7 or Na2Cr2O7 in saline was intravenously administered to rats, two ESR signals due to pentavalent chromium(V) were detectable in the circulating blood of rats. Cr(V) detected in the blood was indicated to be in the CrO(O4) and CrO(S2O2) coordination modes after the study on model complexes. From the changes of ESR signal intensities due to Cr(V) in the blood, the metallokinetic parameters were obtained using the pharmacokinetic analysis and the curve-fitting methods. The obtained results are important for understanding carcinogen chromate in terms of the formation of Cr(V) in animals. In addition, we propose the BCM-ESR method, which is useful to analyze the disposition of paramagnetic metal species in the blood of living animals.
Sakurai
H
H
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan. sakurai@mb.kyoto-phu.ac.jp
Takechi
K
K
Tsuboi
H
H
Yasui
H
H
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002273:Carcinogens / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D002840:Chromates / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D002857:Chromium / Q000097:blood* / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D001798:Blood Proteins; D002273:Carcinogens; D002840:Chromates; D002857:Chromium