| Involvement of Mrp2 in hepatic and intestinal disposition of dinitrophenyl-S-glutathione in partially hepatectomized rats. | |
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MedLine Citation:
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PMID: 15590889 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ability of the liver and small intestine for secretion of dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), into bile and lumen, respectively, as well as expression of Mrp2 in both tissues, were assessed in 70-75% hepatectomized rats. An in vivo perfused intestinal model was used. A single i.v. dose of 30 micromol/kg b.w. of 1-chloro-2,4-dinitrobenzene (CDNB) was administered and its glutathione conjugate, DNP-SG, was determined by HPLC in bile and intestinal perfusate. One and seven days after hepatectomy, biliary excretion of DNP-SG was decreased by 90 and 50% with respect to shams, respectively, when expressed per mass unit. In contrast, intestinal excretion was increased by 63% or unchanged one and seven days post-hepatectomy, respectively. Tissue content of DNP-SG 5 min after CDNB administration was substantially decreased in liver and significantly increased in intestine, one day post-hepatectomy. Western and immunofluorescence studies revealed preserved levels and localization of Mrp2 in both tissues from hepatectomized animals, irrespective of the time analyzed. In spite of preserved expression of Mrp2, the higher availability of DNP-SG in intestinal cells, likely as a consequence of increased glutathione-S-transferase-mediated conjugation of CDNB, may explain the in vivo findings. Further experiments in isolated hepatocytes suggested that decreased synthesis of DNP-SG rather than altered canalicular transport is responsible for the substantial impairment in excretion of this compound into bile. Taken together, these results indicate that the intestine may partially compensate for liver DNP-SG disposition, particularly shortly after surgery, while liver capability is recovering. |
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Authors:
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Silvina S M Villanueva; María L Ruiz; Marcelo G Luquita; Enrique J Sánchez Pozzi; Viviana A Catania; Aldo D Mottino |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2004-12-08 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 84 ISSN: 1096-6080 ISO Abbreviation: Toxicol. Sci. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-02-10 Completed Date: 2005-06-08 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: 4-11 Citation Subset: IM |
Affiliation:
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Institute of Experimental Physiology, National University of Rosario, S2002LRL-Rosario, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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physiology* Animals Bile / metabolism Biological Transport, Active Biotransformation Blotting, Western Densitometry Dinitrochlorobenzene / metabolism Fluorescent Antibody Technique Glutathione / analogs & derivatives*, metabolism* Hepatectomy* Hepatocytes / metabolism Intestines / metabolism* Liver / metabolism* Male Organ Size Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/ATP-Binding Cassette Transporters; 0/Abcc2 protein, rat; 26289-39-4/S-(2,4-dinitrophenyl)glutathione; 70-18-8/Glutathione; 97-00-7/Dinitrochlorobenzene |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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