Linked Life Data

1732517

Source:http://linkedlifedata.com/resource/pubmed/id/1732517

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-2-21
pubmed:abstractText
Several new powerful chelating agents, suitable for the removal of a variety of certain heavy-metal ions from the body by oral application, have been synthesized and tested. Structurally, these compounds are partially lipophilic polyamino carboxylic acids (PACA). They were synthesized in nonaqueous media from triethylenetetramine (TT) by monoalkylation of a primary amino group, followed by exhaustive carboxymethylation of the remaining amino groups using ethyl bromoacetate and subsequent alkaline hydrolysis of the ester. Compounds were characterized using IR, 1H NMR, 13C NMR, and mass spectrometry. Synthesis and testing of two of these compounds, C12- and C22-triethylenetetraminepentaacetic acid (CnTT), is described in detail. Gel permeation chromatography of a mixture of the PACA and actinide elements have shown these substances to be strong chelating agents similar to EDTA or DTPA. They were capable of removing plutonium from contaminated liver cytosol in vitro. In contrast to their nonlipophilic counterparts EDTA and DTPA, the model substances exhibited appreciable absorption from the intestine and, therefore, can be administered orally. With increasing length of the alkyl chain, the chelons can be directed primarily to the liver, one of the target organs for actinide contamination. In vivo, absorption from the ligated duodenum and jejunum of rats after 2 h was 27% of the amount introduced. Compared to untreated controls, daily feeding of 200 mumol of the chelons (C12TT or C22TT)/kg of body weight to rats for 10 days reduced the whole body Am by 29% and 44%, respectively. Am was eliminated most efficiently from the liver, with a reduction of 71% and 89% (p less than 0.001). However, the skeletal retention also was reduced by 17% and 32% from the femora (p less than 0.001) and 20% and 37% from the carcass for the C12TT and C22TT compounds, respectively. No weight loss or other obvious signs of blood, kidney, liver, or intestinal toxicity were observed after the 10-day treatment. These new chelators are promising as agents for oral chelation therapy to remove actinides and possibly other elements from body stores.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
112-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Decorporation of aged americium deposits by oral administration of lipophilic polyamino carboxylic acids.
pubmed:affiliation
Radiobiology Division, School of Medicine, University of Utah, Salt Lake City 84112.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.