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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1990-10-9
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pubmed:abstractText |
A procedure has been developed for estimating the survival time of short-lived alkylating agents in a flow system at physiological temperature and pH. The system simulated the slow release into the bloodstream of a reactive compound formed in the liver. A solution of the reactive compound was injected slowly into a fast stream of aqueous fluid and immediately mixed. After a delay (up to 1 min) determined by a length of tube, during which hydrolysis took place, the surviving reactive compound was trapped on a column of immobilized thiol (thiol-Sepharose), and the fluid was recirculated via a reservoir. The system was used to study the hydrolysis of the pyrrolizidine alkaloid metabolites dehydromonocrotaline, dehydro-anacrotine and dehydroretrorsine. The S-bound pyrrolic moiety in the trap was measured colorimetrically and hydrolysis rates were estimated after a series of 1-h runs with different delay times. Hydrolysis of dehydroretrorsine was very rapid, whereas the hydrolysis of dehydromonocrotaline and dehydro-anacrotine fitted biphasic first-order reactions, with a faster first phase. By isolating and identifying the trapped products from dehydromoncrotaline it was shown that the two phases involved hydrolysis of the 7- and 9-ester groups, respectively. The results supported the view that a proportion of the reactive metabolites from the alkaloids monocrotaline and anacrotine would be able to survive long enough to be transported from the liver to the lungs of a rat. The flow system would be applicable to the study of other types of short-lived metabolites.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkylating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Monocrotaline,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolizidine Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Sepharose,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/dehydroanacrotine,
http://linkedlifedata.com/resource/pubmed/chemical/monocrotaline pyrrole
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pubmed:status |
MEDLINE
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pubmed:issn |
0009-2797
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
76
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19-30
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:2393942-Alkylating Agents,
pubmed-meshheading:2393942-Chemical Phenomena,
pubmed-meshheading:2393942-Chemistry,
pubmed-meshheading:2393942-Equipment Design,
pubmed-meshheading:2393942-Hydrolysis,
pubmed-meshheading:2393942-Kinetics,
pubmed-meshheading:2393942-Monocrotaline,
pubmed-meshheading:2393942-Pyrrolizidine Alkaloids,
pubmed-meshheading:2393942-Sepharose,
pubmed-meshheading:2393942-Sulfhydryl Compounds,
pubmed-meshheading:2393942-Time Factors
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pubmed:year |
1990
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pubmed:articleTitle |
Trapping and measurement of short-lived alkylating agents in a recirculating flow system.
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pubmed:affiliation |
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
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pubmed:publicationType |
Journal Article
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