| Uridine catabolism by the isolated perfused rat liver. | |
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MedLine Citation:
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PMID: 1500698 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A new approach in the treatment of gastrointestinal tumors with 5-fluorouracil involves the infusion of high doses of uridine to improve the chemotherapeutic efficiency of the former. High amounts of uracil formed from uridine can interfere with the hepatic catabolism of 5-fluorouracil and thus increase its bioavailability and toxicity. In our study, we analysed the metabolite pattern of uridine in the effluent of isolated perfused rat livers in relation to portal uridine levels. The livers were perfused hemoglobin-free without recirculation at a constant flow. In the perfusate, uridine was changed from 0.5 to 100 mumol/l. The complete degradation of [2-14C]uridine and [2-14C]uracil was monitored via the release of labeled CO2. Radioactive catabolites of uridine including uracil and the sum of dihydrouracil and beta-ureidopropionate were separated by high-performance liquid chromatography and counted using a radioactivity flow monitor. Portal uridine concentrations were increased from 0.5 to 100 mumol/l and were accompanied by a rise in the relative amount of non-metabolized uridine in the effluent from 13 to 78%. At uridine concentrations above 50 mumol/l, there was a constant release of uracil into the effluent, indicating saturation of uridine phosphorolysis or transport. The amount of 14CO2 formed by the liver reflecting complete uridine breakdown was higher than any other uridine metabolite when uridine concentration varied from 0.5 to 15 mumol/l. Saturation of 14CO2 formation was achieved at a uridine concentration of 25 mumol/l. Higher peak values of 14CO2 release were observed after direct infusion of equivalent amounts of uracil into the portal vein.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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A Holstege; H M Gengenbacher; L Jehle; W Gerok |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hepatology Volume: 14 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 1992 Mar |
Date Detail:
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Created Date: 1992-09-15 Completed Date: 1992-09-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 335-41 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Freiburg, Federal Republic of Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biotransformation Carbon Radioisotopes Chromatography, High Pressure Liquid Kinetics Liver / metabolism* Male Perfusion Rats Rats, Inbred Strains Uracil / metabolism* Uridine / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Carbon Radioisotopes; 58-96-8/Uridine; 66-22-8/Uracil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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