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3,4,3-LIHOPO和二乙三胺五乙酸(DTPA)在模拟伤口被硝酸盐污染后促进大鼠体内钚和镅排泄的比较疗效

Comparative efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat after simulated wound contamination as nitrates.

作者信息

Stradling G N, Gray S A, Moody J C, Pearce M J, Wilson I, Burgada R, Bailly T, Leroux Y, Raymond K N, Durbin P W

机构信息

Laboratoire de Chimie Structurale Biomolécularie, Universite Paris Nord, Bobigny, France.

出版信息

Int J Radiat Biol. 1993 Jul;64(1):133-40. doi: 10.1080/09553009314551191.

Abstract

With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 238Pu and 241Am from the rat after subcutaneous (s.c.) and intramuscular (i.m.) injection of about 200 Bq of each actinide (0.3 ng Pu, 1.6 ng Am). After the s.c. deposition of 238Pu and 241Am, both ligands were more effective after local administration than (in decreasing order) their repeated interperitoneal (i.p.) injection, single i.p. injection and continuous infusion. Dosages of 3 mumol kg-1 of 3,4,3-LIHOPO were at least as effective as 30 mumol kg-1 DTPA after each mode of administration. The most effective regimen of those investigated for s.c. 238Pu and 241Am involved local administration of 30 mumol kg-1 of 3,4,3-LIHOPO at 30 min followed by i.p. injections at 6 h, 1, 2 and 3 day. By day 7 after exposure, the amounts of 238Pu and 241Am retained in the body were 2 and 7% of those in controls, respectively and 10 and four times less than when DTPA was administered using the same regimen. The ligand 3,4,3-LIHOPO was more effective for 238Pu and 241Am after their i.m. injection. This was attributed to the greater retention of these actinides at the wound site (97 versus 67%) when treatment commenced. After a single local injection of 30 mumol kg-1 at 30 min, the amounts of 238Pu and 241Am retained in the body at 7 day were 0.9 and 0.8% of controls. These values were 34 and 27 times less than after local and repeated i.p. injections of DTPA at dosages of 30 mumol kg-1. It is concluded that the administration of 3,4,3-LIHOPO represents potentially a most significant advance in the treatment of wound contamination by 238Pu and 241Am by chelating agents.

摘要

以二乙三胺五乙酸(DTPA)作为对照,对铁载体类似物3,4,3-LIHOPO进行了研究,观察其在皮下(s.c.)和肌肉内(i.m.)注射约200贝克勒尔(Bq)的每种锕系元素(0.3纳克钚,1.6纳克镅)后从大鼠体内清除238Pu和241Am的能力。在皮下注入238Pu和241Am后,两种配体在局部给药后的效果均优于(按降序排列)其重复腹腔内(i.p.)注射、单次腹腔内注射和持续输注。在每种给药方式下,3,4,3-LIHOPO的剂量为3微摩尔/千克时的效果至少与DTPA的剂量为30微摩尔/千克时相同。针对皮下注射238Pu和241Am所研究的最有效方案包括在30分钟时局部给予30微摩尔/千克的3,4,3-LIHOPO,随后在6小时、1天、2天和3天时进行腹腔内注射。到暴露后第7天,体内保留的238Pu和241Am量分别为对照组的2%和7%,比使用相同方案给予DTPA时少10倍和4倍。配体3,4,3-LIHOPO在肌肉内注射238Pu和241Am后更有效。这归因于开始治疗时这些锕系元素在伤口部位的保留率更高(分别为97%和67%)。在30分钟时单次局部注射30微摩尔/千克后,第7天时体内保留的238Pu和241Am量分别为对照组的0.9%和0.8%。这些值比以30微摩尔/千克的剂量局部和重复腹腔内注射DTPA后的结果分别少34倍和27倍。得出的结论是,通过螯合剂给予3,4,3-LIHOPO可能代表了在治疗238Pu和241Am伤口污染方面的一项极其重要的进展。

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