Acute toxicity of subcutaneously administered depleted uranium and the effects of CBMIDA in the simulated wounds of rats.
We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wound model (experiment I), and the effects of a chelating agent, catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA), on the removal and damages caused by uranium by local treatment for wounds in rats (experiment II). Experiment I: To examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg kg-1 DU in a solution of pH 1 and 7. The rats were killed 1, 3, 6, and 24 h after DU injection. The DU (pH 1) injection site on the skin was altered markedly by acid burn, and the chemical action of uranium compared with that of DU (pH 7). After the injection of 4 mg kg-1 DU (pH 1), about 60% of the uranium was retained 1-3 h at the injected sites and then decreased to 16% at 24 h. However, the concentration of uranium in the injected site after 16 mg kg-1 DU (pH 1) injection did not change significantly. Urinary excretion rates of uranium (pH 1) increased in a time-independent manner after the injection. Depositions of uranium in the liver, kidneys and femur were found at 1 h after DU injection, and the results of serum and urinary examinations indicated that severe damage in the organs, including the kidney, was induced. The results of the DU (pH 7) were useful for estimating the chemical toxicity of uranium. Experiment II: The effects of CBMIDA by local treatment for wounds with DU were examined. CBMIDA (480 mg kg-1) was infused into the DU-injected site 0, 10, 30, 60, 120 min, and 24 h after the subcutaneous injection of 4 mg kg-1 DU (pH 1 and 7). The uranium at the injected sites decreased to 4-17% of that at 24 h in the DU (pH 1) group without CBMIDA treatment in experiment I, when it was administered within 120 min after DU injection. In addition, CBMIDA had excellent efficacy in excreting the uranium in urine and feces and decreasing the concentrations of uranium in the kidneys and femur. However, there were no distinct effects of CBMIDA for DU (pH 7). In conclusion, the results indicated that the subcutaneous injected uranium acutely induced severe damage in the DU-injected sites and organs by chemical toxicity within a very short time after DU intake, despite the chemical forms of uranium used, and the local treatment of CBMIDA for wounds contaminated with DU was effective in decreasing the acute toxicity of uranium if carried out within 120 min after DU administration.
Fukuda
Satoshi
S
Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba 263-8555, Japan. s_fukuda@nirs.go.jp
Ikeda
Mizuyo
M
Nakamura
Mariko
M
Yan
Xueming
X
Xie
Yuyuan
Y
D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007279:Injections, Subcutaneous; D007668:Kidney / Q000473:pathology / Q000528:radiation effects; D008099:Liver / Q000528:radiation effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014501:Uranium / Q000493:pharmacokinetics / Q000633:toxicity*; D014947:Wounds and Injuries / Q000473:pathology*
D002396:Catechols; D002614:Chelating Agents; D014501:Uranium; C053731:catechol-3,6-bis(methyleneiminodiacetic acid)