| Galactosamine prevents ethinylestradiol-induced cholestasis. | |
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MedLine Citation:
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PMID: 16554370 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ethinylestradiol (EE) induces intrahepatic cholestasis in experimental animals being its derivative, ethinylestradiol 17beta-glucuronide, a presumed mediator of this effect. To test whether glucuronidation is a relevant step in the pathogenesis of cholestasis induced by EE (5 mg/kg b.wt. s.c. for 5 consecutive days), the effect of simultaneous administration of galactosamine (200 mg/kg b.wt. i.p.) on biliary secretory function was studied. A single injection of this same dose of galactosamine was able to decrease hepatic UDP-glucuronic acid (UDP-GA) levels by 85% and excretion of EE-17beta-glucuronide after administration of a tracer dose of [3H]EE by 40%. Uridine (0.9 g/kg b.wt. i.p.) coadministration reverted the effect of galactosamine on hepatic UDP-GA levels and restored the excretion of [3H]EE-17beta-glucuronide. When administered for 5 days, galactosamine itself did not alter any of the serum markers of liver injury studied (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) or biliary secretory function. When coadministered with EE, galactosamine partially prevented the impairment induced by this estrogen in total bile flow, the bile-salt-independent fraction of bile flow, basal bile salt secretion, and the secretory rate maximum of tauroursodeoxycholate. Uridine coadministration partially prevented galactosamine from exerting its anticholestatic effects. In conclusion, galactosamine administration partially prevented EE-induced cholestasis by a mechanism involving decreased UDP-GA availability for subsequent formation of EE 17beta-glucuronide. The evidence thus supports the hypothesis that EE 17beta-glucuronide is involved in the pathogenesis of EE cholestasis. |
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Authors:
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Fernando A Crocenzi; José M Pellegrino; Viviana A Catania; Marcelo G Luquita; Marcelo G Roma; Aldo D Mottino; Enrique J Sánchez Pozzi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-03-22 |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 34 ISSN: 0090-9556 ISO Abbreviation: Drug Metab. Dispos. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-19 Completed Date: 2006-07-31 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: United States |
Other Details:
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Languages: eng Pagination: 993-7 Citation Subset: IM |
Affiliation:
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Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Suipacha 570 (2000) Rosario, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / chemistry, drug effects*, physiology Cholestasis / chemically induced, metabolism, prevention & control* Ethinyl Estradiol* / analogs & derivatives, analysis, metabolism, toxicity Galactosamine / pharmacology* Liver / drug effects*, metabolism Male Rats Rats, Wistar Taurochenodeoxycholic Acid / metabolism Uridine / pharmacology Uridine Diphosphate Glucuronic Acid / antagonists & inhibitors, metabolism |
| Chemical | |
Reg. No./Substance:
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0/ethinyl estradiol glucuronide; 14605-22-2/tauroursodeoxycholic acid; 2616-64-0/Uridine Diphosphate Glucuronic Acid; 516-35-8/Taurochenodeoxycholic Acid; 57-63-6/Ethinyl Estradiol; 58-96-8/Uridine; 7535-00-4/Galactosamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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