| Comparison of synthetic saponin cholesterol absorption inhibitors in rabbits: evidence for a non-stoichiometric, intestinal mechanism of action. | |
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MedLine Citation:
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PMID: 10064735 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hypocholesterolemic activities of pamaqueside and tiqueside, two structurally similar saponins, were evaluated in cholesterol-fed rabbits. The pharmacological profiles of the saponins were virtually identical: both dose-dependently decreased the intestinal absorption of labeled cholesterol 25-75%, increased fecal neutral sterol excretion up to 2.5-fold, and decreased hepatic cholesterol content 10-55%. High doses of pamaqueside (>5 mg/kg) or tiqueside (>125 mg/kg) completely prevented hypercholesterolemia. Decreases in plasma and hepatic cholesterol levels were strongly correlated with increased neutral sterol excretion. Ratios of neutral sterol excreted to pamaqueside administered were greater than 1:1 at all doses, in opposition to the formation of a stoichiometric complex previously suggested for tiqueside and other saponins. Ratios in tiqueside-treated rabbits were less than unity, a reflection of its lower potency. Pamaqueside-treated rabbits exhibited a more rapid decline in plasma cholesterol concentrations than control animals fed a cholesterol-free diet, indicating that the compound also inhibited the absorption of biliary cholesterol. Intravenous administration of pamaqueside had no effect on plasma cholesterol levels despite plasma levels twice those observed in rabbits given pamaqueside orally. These data indicate that pamaqueside and tiqueside induce hypocholesterolemia by blocking lumenal cholesterol absorption via a mechanism that apparently differs from the stoichiometric complexation of cholesterol hypothesized for other saponins. |
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Authors:
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L A Morehouse; F W Bangerter; M P DeNinno; P B Inskeep; P A McCarthy; J L Pettini; Y E Savoy; E D Sugarman; R W Wilkins; T C Wilson; H A Woody; L M Zaccaro; C E Chandler |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Journal of lipid research Volume: 40 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 1999 Mar |
Date Detail:
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Created Date: 1999-04-13 Completed Date: 1999-04-13 Revised Date: 2009-11-03 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 464-74 Citation Subset: IM |
Affiliation:
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Department of Cardiovascular and Metabolic Diseases, Pfizer Central Research, Eastern Point Road, Groton, CT 06340, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Anticholesteremic Agents / pharmacology Bile / metabolism Cholesterol / blood Cholesterol, Dietary / metabolism* Cholesterol, HDL / blood Feces / chemistry Hypercholesterolemia / metabolism Injections, Intravenous Intestinal Absorption / drug effects* Liver / metabolism Male Molecular Structure Rabbits Saponins / pharmacology* Sterols / analysis |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Cholesterol, Dietary; 0/Cholesterol, HDL; 0/Saponins; 0/Sterols; 0/pamaqueside; 57-88-5/Cholesterol; 99759-19-0/tiqueside |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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