Toxicity of uranium and the removal effects of CBMIDA and EHBP in simulated wounds of rats.
We examined the acute toxicity of uranium (99.3% 238U, 0.7% 235U) and the effects of Catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) and Ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on the removal of uranium after intramuscular injection as a simulated wound intake in rats. In this experiment, male Wistar rats, 8 wk old, were injected intramuscularly with uranyl nitrate in the femoral muscles. Experiment I: Rats died from 3 to 7 d after they were injected with five doses of 7.9, 15.8, 31.5, 63, and 126 mg kg(-1) uranium. The uranium retained 8.4-13.6% of the injected doses in the kidneys, showing the relationship between the injected dose and the retained concentration (r = 0.997). The excretion rates of the injected doses in the 63 and 126 mg kg(-1) uranium-injected rats were 1.73% and 3.09% in urine and 0.81% and 1.06% in feces on the first day, and 0.54% and 0.56% in feces on the second day, respectively. Experiment II: The retention of uranium at 1, 3, 6, and 24 h was examined after rats were injected with 63 mg kg(-1) uranium. The concentration of uranium decreased in the plasma, while it increased in the kidneys and femur until 6 h, and it continued to increase in the liver until 24 h. Experiment III: Rats were divided into four groups (n = 10) and were injected with a dose of 2 mg kg(-1) uranium. Two of the groups were then injected intraperitoneally with 240 or 480 mg kg-1 CBMIDA, and one group was injected with 10 mg kg(-1) EHBP once daily for 28 d, beginning 1 h after uranium injection on the first day. The fourth group was the non-treated control group. The survival rates at the end of the experiment were 80% and 40% in the 240 and 480 mg kg(-1) CBMIDA groups, 50% in the EHBP group, and 20% in the non-treated group. The successive administration of chelating agents was effective in decreasing the concentration of uranium in the kidneys, bone, and liver. The results indicated that uranium induces acute death and renal dysfunction by chemical toxicity, and both CBMIDA and EHBP were effective agents to prevent these effects.
Fukuda
Satoshi
S
Research Center for Radiation Emergency Medicine and International Space Radiation Laboratory, National Institute of Radiological Sciences, Chiba 263-8555 Japan. s_fukuda@nirs.go.jp
Iida
Haruzo
H
Ikeda
Mizuyo
M
Yan
Xueming
X
Xie
Yuyuan
Y
D000818:Animals; D002396:Catechols / Q000008:administration & dosage*; D002614:Chelating Agents / Q000008:administration & dosage; D015913:Chelation Therapy / Q000379:methods*; D004164:Diphosphonates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005547:Foreign Bodies / Q000150:complications / Q000378:metabolism; D007273:Injections, Intramuscular; D008571:Men; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009928:Organ Specificity; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D011835:Radiation Protection / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D013534:Survival; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome; D014501:Uranium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000506:poisoning*; D014950:Wounds, Penetrating / Q000150:complications / Q000378:metabolism
D002396:Catechols; D002614:Chelating Agents; D004164:Diphosphonates; C409217:ethane-1-hydroxy-1,1-bisphosphonate; D014501:Uranium; C053731:catechol-3,6-bis(methyleneiminodiacetic acid)