| Simulation of trichloroacetic acid kinetics in the isolated perfused rat liver using a biologically based kinetic model. | |
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MedLine Citation:
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PMID: 12388832 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Trichloroacetic acid (TCA) is a contaminant of drinking water. It induces peroxisome proliferation in livers of rats and mice and is hepatocarcinogenic in the latter species. Previous experimental studies of the kinetics of TCA in the isolated perfused rat liver (IPRL) at two doses have been reported. To gain more insight into the mechanistic processes controlling TCA kinetics in the liver a biologically based kinetic (BBK) model for the IPRL was used to analyze the experimental data. The IPRL was exposed to 25, 250, or 1000 microM TCA for 2 h in a recirculating perfusion system. These doses were not cytotoxic. The BBK model simulated the TCA concentration in perfusion medium and liver, and the biliary excretion of TCA. Separate protein binding studies showed that over 90% of TCA was bound to albumin in the perfusion medium whereas binding in liver homogenate was much lower. Integrating the information on protein binding into the BBK model, the hepatic uptake of TCA and its biliary excretion could be fitted assuming asymmetrical saturable transport at the sinusoidal membrane and linear transport at the bile canalicular membrane. To validate the BBK model, additional washout experiments were conducted in which the perfusion medium was replaced with TCA-free medium after 30 min of exposure of the liver to 1000 microM TCA. This approach illustrates the usefulness of BBK modeling for analyzing experimental kinetic data and gaining insight in kinetic mechanisms controlling the behavior of a chemical in the liver. |
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Authors:
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Corike Toxopeus; J M Frazier |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 70 ISSN: 1096-6080 ISO Abbreviation: Toxicol. Sci. Publication Date: 2002 Nov |
Date Detail:
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Created Date: 2002-10-21 Completed Date: 2003-05-08 Revised Date: 2010-09-17 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 27-39 Citation Subset: IM |
Affiliation:
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McLaughlin Research Institute, Great Falls, Montana 59405, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism* Bile Canaliculi / metabolism Biological Transport Cattle Liver / metabolism* Male Models, Biological Protein Binding Rats Rats, Inbred F344 Serum Albumin, Bovine / metabolism Trichloroacetic Acid / pharmacokinetics* Water Pollutants, Chemical / pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Serum Albumin, Bovine; 0/Water Pollutants, Chemical; 76-03-9/Trichloroacetic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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