title: Effects of pH on du intake and removal by CBMIDA and EHBP.
abstract: The effects of pH on deleted uranium (DU) and DU removal by chelating agents, catechol-3,6-bis(methyleneiminodiacetic acid) (CBMIDA) and ethane-1-hydroxy-1,1-bisphoshonate (EHBP) in rats were examined. Ninety male Wistar rats, 8 wk old, were divided into six groups of 15 rats. Rats of five groups were each preinjected intraperitoneally with 8 mg kg(-1) DU in pH 1, 3, 5, 7, and 10 solutions. In each pH group, five rats were injected intraperitoneally with 240 mg kg(-1) CBMIDA, and the other five with 10 mg kg(-1) EHBP; the remaining five were used as the corresponding group with no chelating agent. One group was kept as the control (no injected DU) group, which consisted of five intact, five with CBMIDA, and five with EHBP administration. Chelating agents were administered for 3 d. Rats were injected with the DU 30 min prior to treatment with chelating agents on the first day. The gathered data indicated that the DU toxicity varied according to differences in pH; in addition, at pH 7, when varied DU-complexes formed, the DU toxicity including renal dysfunction increased, and the DU removal effects of chelating agents were not obtained. Both CBMIDA and EHBP were effective in excreting DU, reducing DU concentrations in organs, and preventing DU-induced toxicity, and CBMIDA was superior to EHBP, particularly in the prevention of renal dysfunction. These results indicate that the excretion and distribution of soluble DU changes and the removal effects of chelating agents according to pH differs, indicating that the treatment with chelating agent should begin in the DU-contaminated person as early as possible after an accident.
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba 263-8555, Japan. s_fukuda@nirs.go.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.forename: Mizuyo
authors.initials: M
authors.lastname: Ikeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Xueming
authors.initials: X
authors.lastname: Yan
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D002396:Catechols / Q000008:administration & dosage*; D002614:Chelating Agents / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D005243:Feces / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects; D014501:Uranium / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002396:Catechols; D002614:Chelating Agents; D004164:Diphosphonates; D011837:Radiation-Protective Agents; C409217:ethane-1-hydroxy-1,1-bisphosphonate; D014501:Uranium; C053731:catechol-3,6-bis(methyleneiminodiacetic acid)