| Ursodeoxycholate-induced hypercholeresis in cirrhotic rats: further evidence for cholehepatic shunting. | |
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MedLine Citation:
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PMID: 7927207 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of the investigation was to explore whether ursodeoxycholate, a tertiary bile acid with potential for treatment of chronic cholestasis in cirrhotic liver disease, has the same physiological effects in cirrhotic as in normal rats. Furthermore, we wanted to investigate whether ductular proliferation, as it occurred in this situation, increases the bicarbonate stimulatory effect of ursodeoxycholate. Rats (n = 16) were rendered cirrhotic by continuous exposure to phenobarbital-carbon tetrachloride; untreated animals (n = 13) served as controls. In cirrhotic rats in vivo, ursodeoxycholate (20 mumoles/min/kg) stimulated bile salt secretion and bile flow less than in controls. Nevertheless, the increment in ursodeoxycholate-induced biliary bicarbonate--the bicarbonate stimulatory potency--was increased by 29% in cirrhotic animals (0.55 +/- 0.08 mmol vs. 0.71 +/- 0.11 mmol; p < 0.05). This finding could be related to ductular proliferation because the volume fraction of bile ductules, determined stereologically, increased from 0.3% +/- 0.1% to 2.7% +/- 0.6% in cirrhotic rats (p < 0.005). To explore further the behavior of ductules during ursodeoxycholate stimulation, we carried out experiments in the in situ perfused rat liver. In the portally perfused organ, replacement of bicarbonate by tricine-acetate abolished ursodeoxycholate-induced hypercholeresis. In the dually perfused organ (perfusion of both portal vein and hepatic artery) perfusion of the hepatic artery with bicarbonate-containing buffer, ursodeoxycholate had a similar stimulatory effect as in vivo in both control and cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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C Elsing; H Sägesser; J Reichen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 20 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 1994 Oct |
Date Detail:
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Created Date: 1994-10-28 Completed Date: 1994-10-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1048-54 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, University of Berne, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Bicarbonates / metabolism Bile / physiology, secretion* Bile Acids and Salts / secretion Bile Ducts / pathology Carbonic Anhydrases / physiology Electrolytes / metabolism Erythritol / diagnostic use, pharmacokinetics Hyperplasia Liver / drug effects*, pathology Liver Cirrhosis, Experimental / pathology, physiopathology* Male Perfusion / methods Rats Rats, Sprague-Dawley Regression Analysis Ursodeoxycholic Acid / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Bicarbonates; 0/Bile Acids and Salts; 0/Electrolytes; 128-13-2/Ursodeoxycholic Acid; 149-32-6/Erythritol; EC 4.2.1.1/Carbonic Anhydrases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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