中国药理学与毒理学杂志2023，Vol.37Issue(12)：923-927,5.DOI:10.3867/j.issn.1000-3002.2023.12.005
新型促排剂NBED对铀的促排效果及机制
Effect and mechanism of NBED on uranium excretion
摘要
Abstract
OBJECTIVE To study the effect and mechanism of N1,N2 bis(2,3-dihydroxy-4,6-disul-fonic acid benzyl)ethylenediamine sodium salt(NBED)on uranium excretion.METHODS ICR mice were divided into the blank control group,uranium exposure group(0.03 mg·mouse-1),uranium expo-sure+diethylenetriamine pentaacetic acid(DTPA-CaNa3)(150 mg·kg-1)group,and the uranium expo-sure+NBED(45,90,180 mg·kg-1)group.After uranyl acetate was injected into the tail vein of mice,appro-priate doses of NBED or DTPA-CaNa3 were injected into the tail vein.After 24 h,the uranium contents in the kidney,bone and liver+spleen+muscle were determined by inductively coupled plasma mass spectrometry(ICP-MS).The dissociation constant of NBED and the complexation constant of NBED with uranyl were determined via potentiometric titration.RESULTS Animal experiments showed that NBED 45,90 and 180 mg·kg-1 could significantly reduce the uranium accumulation in the kidney by 48.2%-66.5%,in the bone by 21.4%-54.8%,and in liver+spleen+muscle by 38.2%(P<0.01),compared to the uranium exposure group,47.8%,21.4%and 22.7%respectively by DTPA-CaNa3(P<0.05),and the effect in the NBED 180 mg·kg-1 group was significantly better than in the DTPA-CaNa3 group(P<0.05).The results of potentiometric titration showed that there was about 22.3%LH5,59.8%LH4 and 17.85%LH3(L means NBED)in NBED at pH 7.4,and the secondary dissociation LH4 was the main form.In the range of pH 3-11,there were four complex compounds of NBED and uranyl,and their step-wise complex cumulative constants were logβ111(12.5),logβ101(9.8),logβ102(15.3),logβ1-12(6.5)respectively.The(UO2)L22-was the main species(75.3%)at physiological pH 7.4,and the-log[UO22+free]value(pUO2)of free uranyl ion in solution was 9.57.CONCLUSION NBED mainly exists in the form of secondary dissociated LH4in vivo,and chelates with uranyl 2:1 to form uranyl complex,which is excreted in vitro.Intravenous administration of NBED can more effectively promote excretion than DTPA-CaNa3.关键词
促排剂/NBED/醋酸铀酰/解离常数/络合常数Key words
decorporation agent/NBED/uranyl acetate/dissociation constant/stability constant分类
药学引用本文复制引用
张梦丹,周文华,龚佳格,李鹏,高洁,李建国..新型促排剂NBED对铀的促排效果及机制[J].中国药理学与毒理学杂志,2023,37(12):923-927,5.基金项目
十三五后处理专项(HC17110217) Special Project for Post-Processing of the 13th Five-Year Plan(HC17110217) （HC17110217）
