Monohydroxy bile salt sulfates: tauro-3 beta-hydroxy-5-cholenoate-3-sulfate induces intrahepatic cholestasis in rats
The biologic effects of sulfation of tauro-3 beta-hydroxy-5-cholenoate and of taurolithocholate were compared. Equimolar amounts (100 nmol/min X 100 g body wt) of the following were administered intravenously to male Sprague-Dawley rats over a 180-min period: taurolithocholate, (/sup 14/C)taurolithocholate-3-sulfate, tauro-3 beta-hydroxy-5-cholenoate, (/sup 14/C)tauro-3 beta-hydroxy-5-cholenoate-3-sulfate, its combination with taurocholate, and a saline-albumin solution (control). Sulfation of taurolithocholate and of tauro-3 beta-hydroxy-5-cholenoate only prevented the cholestatic effect of the former. Bile flow during infusion of (/sup 14/C)tauro-3 beta-hydroxy-5-cholenoate-3-sulfate was reduced by 80% at the end of the experiment. A dose-dependent bile flow reduction was demonstrated. Recovery of the administered bile acid was 3% in urine, 13% in serum, 23% in the liver tissue, and 52% in bile, respectively. Excretion of biliary cholesterol and phospholipids was significantly reduced during the first hour of infusion. Coadministration of taurocholate abolished the cholestatic effect and enhanced the renal excretion of the sulfated bile salt. These data suggest that (a) the cholestatic effect of tauro-3 beta-hydroxy-5-cholenoate-3-sulfate is comparable with or may even exceed the effect of taurolithocholate and (b) although sulfation renders some bile salts more water soluble, it does not prevent the cholestatic effect of all monohydroxy bile salts.
- Research Organization:
- Department of Clinical Pharmacology, University of Berne, Switzerland
- OSTI ID:
- 5533645
- Journal Information:
- Gastroenterology; (United States), Journal Name: Gastroenterology; (United States) Vol. 85:3; ISSN GASTA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
BILE ACIDS
BILIARY TRACT
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD SERUM
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHOLESTEROL
CLEARANCE
DIGESTIVE SYSTEM
ESTERS
EXCRETION
FLOW BLOCKAGE
HYDROXY COMPOUNDS
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MATERIALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHOLIPIDS
RATS
RENAL CLEARANCE
RODENTS
STEROIDS
STEROLS
SULFONIC ACIDS
TAURINE
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES