Efficacy of oral and intraperitoneal administration of CBMIDA for removing uranium in rats after parenteral injections of depleted uranium.
The efficacy of oral administration of the chelating agent catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) for removing uranium from rats after intraperitoneal (i.p.) and intramuscular (i.m.) injections of depleted uranium (DU) was examined and the results with those by the i.p. injection of CBMIDA were compared. In Experiment 1, after a single i.p. injection of 8 mg kg(-1) of DU of rat's body weight, 35 8-week-old male rats were divided into seven groups consisting of five rats each. Three groups were administered with CBMIDA 240, 720 or 1200 mg kg(-1) of rat's body weight orally once a day, and three other groups received an i.p. injection of 240, 480 or 720 mg kg(-1) CBMIDA for 3 d, starting 30 min after DU injection on the first day. One DU group received no CBMIDA. The remaining five intact rats were used as a control group. Rats were killed 6 d after DU injection. In Experiment 2, the 35 male rats that received a single i.m. injection of 8 mg kg(-1) DU were divided into seven groups, and the rats of each group received the same doses of CBMIDA on the same schedules of treatment as those described in Experiment 1. The results obtained in Experiment 1 indicated that orally administered CBMIDA significantly increased the excretion of uranium at doses of 720 and 1200 mg kg(-1) and decreased uranium concentrations, particularly in the kidney, at all the doses tested, and the effects were almost equal to those of the i.p. injection. The lack of increases in creatinine and blood urea nitrogen in serum indicated that CBMIDA is efficacious in preventing the renal dysfunction caused by uranium. In Experiment 2, oral administration of CBMIDA significantly increased uranium excretion and significantly decreased uranium concentrations, particularly in the kidneys, at all the doses tested, and the effects were almost equal to those of the i.p. injection. However, these effects of CBMIDA on the i.m.-injected DU were lower than those of the i.p.-injected DU in Experiment 1. These results indicated that oral administration of CBMIDA has almost the same efficacy as that administered by the parenteral route. Additional study is necessary to obtain satisfactory effects for the clinical use of CBMIDA, particularly for wounds contaminated accidentally with uranium.
Fukuda
S
S
Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. s_Fukuda@nirs.go.jp
Ikeda
M
M
Nakamura
M
M
Yan
X
X
Xie
Y
Y
D000284:Administration, Oral; D000818:Animals; D002396:Catechols / Q000008:administration & dosage*; D002614:Chelating Agents / Q000008:administration & dosage; D007263:Infusions, Parenteral; D008297:Male; D011835:Radiation Protection / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D014501:Uranium / Q000008:administration & dosage / Q000302:isolation & purification* / Q000493:pharmacokinetics*
D002396:Catechols; D002614:Chelating Agents; D014501:Uranium; C053731:catechol-3,6-bis(methyleneiminodiacetic acid)