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EHRLICH II-2nd World Conference on Magic Bullets

16th ICOC

16th ICOC

The toxicities and effects of CBMIDA and EHBP on removal of depleted uranium (DU) by intramuscular injection in the femoral muscles as simulated wounds in rats were examined in Experiment I~III. Male rats, 8 weeks old, were used. Experiment I: Rats were injected intramuscularly with 7.9, 15,8, 31.5, 63 and 126mg/kg depleted uranium. All rats died from 3~7 days after injection. The concentrations of DU in the kidneys were 8.4-16.6% of injected doses (r=0.997). In the rats injected with 63, 126 mg/kg, the urinary excretion of DU was observed at first day, and the feces excretion was for 2 days, but did not observed at third day. Total amount of excreted DU for 3 days were 3.4 % and 4.9% of the injected doses. Experiment II: Rats were injected with 63 mg/kg DU, and then killed 1, 3, 6 and 24 hours to know the retention. The concentration of DU decreased rapidly in the serum, while increased in the kidneys and liver until 6 hours after injection, and continued to increase in the femur until 24 hours. Experiment III: Forty rats were injected intramuscularly with 2mg/kg DU, and divide into four groups; G1) non-treated, G2) 0.48mg/kg CBMIDA, G3) 0.24mg/kg CBMIDA, and G4) 10mg/kg EHBP. The chelating agents were administered intraperitoneally once everyday for 28 days. Rats died for firs 10 days in the G1~3, and for 14 days in the G4. The survival rates at the end of experiment were 20% in the G1, 40% in the G2, 80% in the G3 and 50% in the G4. The rapid decreases in body weights were observed for first 10 days. The concentrations of DU in the organs in the G2-4 were observed. Abnormal values in blood examination were observed in G1-4, and BUN and creatinine were elevated. The results indicated that the lethal dose of DU by intramuscular injection was toxic over 7.9 mg/kg, and the DU retained rapidly in the kidneys, a target organ, and did not excreted after 2 days. CBMIDA and EHBP were effective to increase survival rates by removing DU in the kidneys and other organs., 7th International Symposium on Chelating Agents in Biomedicine Toxicology and Therapeutics

Effects of long-term of Zn-DTPA and CBMIDA administration on reducing plutonium-induced tumors and shortening of life span in rats were examined. Two hundred eighty female rats were divided into four groups (n=40): rats of six groups were injected intraperitoneally with 0.185, 0.37 or 3.7 x105 Bq/kg of plutonium, and once 30 mmol/kg of Ca-DTPA for the first 3 days and then replace to oral administration of daily 30 mmol/kg Zn-DTPA in drinking water. The 0.185 and 0.37 x105 Bq/kg of plutonium are dose to induce frequently tumors, and 3.7 x105 Bq/kg is dose to occur early death before tumors induction. Rats of one group were injected intraperitoneally with 0.37 x105 Bq/kg of plutonium and once 30 mmol/kg of CBMIDA for the first 3 days and replace to daily 30 mmol/kg of CBMIDA in drinking water. All rats were bred until they died. The lengths of life span in the all groups that chelating agents were administered were prolonged compared to those of non-treated groups. In the 0.37 x105Bq/kg of plutonium groups, life span of Zn-DTPA group was longer than that of CBMIDA group. In the anatomical findings, incidence of bone tumors in the 0.185 and 0.37 x105 Bq/kg of plutonium groups reduced to 0 % from 10.5 and 12.5 % of non-treated groups, but increased to 12.5 % from 0 % in the 3.7 x105 Bq/kg. Those of liver reduced to 0% from 2.5 % in the Zn-DTPA but increased to 12 % in 0.37 x105 Bq/kg, and increased to 12% from 2.5 % in the 3.7 x105 Bq/kg group. We demonstrated that a long-term administration of Zn-DTPA and CBMIDA were effective to prevent the shortening of life span in the all plutonium-administered groups, and the induction of tumors in the low dose plutonium groups, but to increase tumors probably due to reduction of plutonium to the ranges that rather occur tumors and prolong of life span in the group that administered high dose of plutonium., 7th International Symposium on Chelating Agents in Biomedicine Toxicology and Therapeutics

The effects of long-term administration of Zn-DTPA (diethyene-triamine-penta-actic acid) and CBMIDA [Catechol-3,6-bis(methyleiminodiaetic acid)] on plutonium-induced bone tumors and shortening of life span in rats were examined. One-hundred-twenty female rats were injected with doses of 18.5, 37, and 370 kBq/kg of plutonium-239. A daily intrperitoneally injected dose of 30 mmol/kg Ca-DTPA was administered to each of 40 rats of the 18.5, 37, and 370 kBq/kg of plutonium groups for first three days followed by the same dose of Zn-DTPA in orally administered in dinking water, while another 40 rats injected with 37 kBq/kg of plutonium were injected intraperitoneally with 30 mmol/kg CBMIDA for the first three days followed by oral administration. High urinary excretion of plutonium was observed for 14-21 days after plutonium injection in the chelating agent-treated groups. In the Zn-DTPA and CBMIDA treated groups, the mean life spans were significantly more prolonged compared with each corresponding (plutonium-injected) group. The incidences of bone tumors in the Zn-DTPA groups were reduced to zero from 10% in the 18.5 and 37 kBq/kg plutonium groups, while they increased to 10% from zero in the 370 kBq/kg plutonium group. The results indicated that human doses of Zn-DTPA and CBMIDA were effective in reducing plutonium-induced effects such as the shortening of life span and the induction of bone tumors in rats., 11th International Congress of the International Radiation Protection Association