Intestinal absorption of lithocholic acid sulfates in the rat: inhibitory effects of calcium
Sulfation of lithocholic acid has been proposed as a mechanism for elimination of this hepatotoxic bile acid from the body by accelerating its fecal excretion. However, quantitative data on the absorption characteristics of sulfated lithocholic acid conjugates in vivo are scarce. We studied the intestinal absorption of /sup 14/C-labeled glycolithocholic acid (GLC), taurolithocholic acid (TLC), and their 3 alpha-sulfate esters, SGLC and STLC, respectively. Studies were performed in unanesthetized rats with a permanent biliary drainage. At an intestinal infusion rate of 125 nmol/min, which is comparable to 7% of the normal biliary bile acid output in the rat, the absorption of sulfated lithocholic acid conjugates was delayed when compared with their unsulfated precursors but quantitatively only slightly reduced over a 24-h period: SGLC 90.9 +/- 3.6%, GLC 94.4 +/- 1.1%, STLC 84.4 +/- 3.0%, and TLC 94.2 +/- 2.1%. Urinary excretion of sulfated and unsulfated bile acids was similar and never exceeded 2% of the dose. SGLC absorption was dose dependent, was not altered by coinfusion of rat bile, and was only slightly reduced by a sixfold overdose of taurocholic acid. SGLC and STLC were excreted into bile largely unchanged in form. In contrast, GLC and TLC were extensively metabolized to more polar bile acids, predominantly to beta-muricholic acid conjugates. Replacement of NaCl in the infusion fluid by CaCl2 reduced the absorption of SGLC and STLC by 63 and 52%, respectively. This calcium effect was less pronounced for the unsulfated bile acids: GLC -22%, and TL-19%. Absorption of taurocholic acid was unaffected by CaCL2.
- Research Organization:
- Univ. of Groningen, The Netherlands
- OSTI ID:
- 5092911
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States)
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BILE ACIDS
EXCRETION
INTESTINAL ABSORPTION
CALCIUM
BIOLOGICAL EFFECTS
BILE
BILIARY TRACT
CARBON 14 COMPOUNDS
RATS
TRACER TECHNIQUES
ABSORPTION
ALKALINE EARTH METALS
ANIMALS
BIOLOGICAL MATERIALS
BODY FLUIDS
CARBOXYLIC ACIDS
CLEARANCE
DIGESTIVE SYSTEM
ELEMENTS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RODENTS
STEROIDS
STEROLS
UPTAKE
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques
560305 - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)