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3,4,3-锂高铁氧还蛋白和二乙三胺五乙酸对促进大鼠体内钚和镅排泄的效果:与其他铁载体类似物的比较

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

作者信息

Stradling G N, Gray S A, Ellender M, Moody J C, Hodgson A, Pearce M, Wilson I, Burgada R, Bailly T, Leroux Y G

机构信息

National Radiological Protection Board, Didcot, Oxon, UK.

出版信息

Int J Radiat Biol. 1992 Oct;62(4):487-97. doi: 10.1080/09553009214552381.

Abstract

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.

摘要

以二乙三胺五乙酸(DTPA)作为对照,对名为3,4,3-LIHOPO的铁载体类似物进行了测试,以研究其在大鼠吸入或静脉注射硝酸钚和镅后清除这两种物质的能力。对于吸入钚的情况,最有效的治疗方案是重复给予30 μmol/kg的3,4,3-LIHOPO。暴露7天后,肺部和全身的钚含量分别降至未治疗动物的2%和4%。这些数值分别比采用相同方案给予DTPA时低六倍和三倍。对于吸入镅的情况,3,4,3-LIHOPO和DTPA被认为效果相当,肺部和全身的含量分别降至对照动物的13%和10%。在重复给予30 μmol/kg的3,4,3-LIHOPO后,一些动物的肝脏和肾脏近端小管出现了轻微的退行性变化;然而,这些变化不如DTPA治疗后明显。静脉注射钚后,最有效的方案是单次给予3 μmol/kg的3,4,3-LIHOPO。7天时的全身含量降至对照的7%,而重复给予30 μmol/kg的DTPA后为19%。在剂量为30 μmol/kg时,由于钚在肝脏中的保留率较高,3,4,3-LIHOPO的效果较差。重复给予30 μmol/kg的3,4,3-LIHOPO对镅的促排效果比DTPA更好;全身含量分别为对照的16%和31%。重要的是,单次给予3 μmol/kg后,全身含量仍降至对照的28%。配体3,4,3-LIHOPO也优于其他铁载体类似物,可能代表了钚和镅促排方面的一项重大进展。

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