| Disposition of isosteviol in the rat isolated perfused liver. | |
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MedLine Citation:
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PMID: 20082626 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. The aim of the present study was to investigate the mechanisms involved in the clearance of isosteviol using the rat isolated perfused liver. 2. Six livers from male Sprague-Dawley rats were perfused with 15.7 mumol isosteviol in a recirculating system. Perfusate and bile samples were collected for 60 min and the liver was collected at the end of the perfusion. All samples collected were incubated with alpha-glucuronidase. Isosteviol-glucuronide was determined as equivalent isosteviol. Isosteviol concentrations were determined using a previously developed liquid chromatography-tandem mass spectrometry method. The final isosteviol liver/perfusate (L/P), bile/liver (B/L) and isosteviol-glucuronide in bile/liver (B(G)/L(G)) ratios were determined. 3. Isosteviol has a high clearance (21.4 +/- 4.8 mL/min) from the perfusate, with a short half-life (13 +/- 4 min). alpha-Glucuronidase incubation revealed that isosteviol is conjugated in the liver and excreted into the bile. There was no isosteviol-glucuronide detected in perfusate samples. The total recovery of the rat isolated perfused liver system is 74 +/- 14% and glucuronidated isosteviol accounted for 23 +/- 4% of the administered dose. 4. In conclusion, we are the first to characterize the metabolism of isosteviol using rat isolated liver perfusion. Our results strongly suggest that the liver is the main organ of isosteviol elimination and that isosteviol is glucuronidated in the liver before it is excreted into the bile. |
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Authors:
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Hongping Jin; Jiping Wang; Jacobus P Gerber; Andrew K Davey |
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Publication Detail:
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Type: In Vitro; Journal Article Date: 2010-01-17 |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: 37 ISSN: 1440-1681 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-06-09 Completed Date: 2010-10-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
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Languages: eng Pagination: 593-7 Citation Subset: IM |
Affiliation:
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Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia 5000, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism Chromatography, Liquid Diterpenes, Kaurane / chemistry, metabolism, pharmacokinetics* Glucosides / metabolism Glucuronides / metabolism Glycoside Hydrolases / pharmacology Liver / metabolism* Male Metabolic Clearance Rate Molecular Structure Perfusion Rats Rats, Sprague-Dawley Tandem Mass Spectrometry Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Diterpenes, Kaurane; 0/Glucosides; 0/Glucuronides; 0/isosteviol; 57817-89-7/stevioside; EC 3.2.1.-/Glycoside Hydrolases; EC 3.2.1.139/alpha-glucuronidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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