PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “BILE ACIDS AND SALTS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

Acid and bile-salt stress of enteropathogenic Escherichia coli enhances adhesion to epithelial cells and alters glycolipid receptor binding specificity.

BACKGROUND: Enteropathogenic Escherichia coli (EPEC), a diarrheagenic pathogen, is exposed to stress during ingestion, and yet little is known about the impact of stress on EPEC-host cell adhesion. METHODS: EPEC adhesion to human epithelial cells was assessed by plate-count assay before and after bacterial stress. Stress treatments included exposure to low pH (with or without acid adaptation) and exposure to physiological concentrations of 4 intestinal bile salts. Expression of bacterial adhesins after stress was assessed by immunoblot and flow-cytometric analysis. Bacteria-lipid binding was determined by thin-layer chromatography overlay assay. RESULTS: Brief low-pH stress (with or without acid adaptation) and bile-salt stress resulted in significantly increased EPEC-host cell adhesion. Erythromycin pretreatment eliminated the adhesion enhancement, suggesting that protein synthesis was required. Immunoblot and flow-cytometric analysis indicated little change in expression of known adhesins after either stress. However, we found increased surface expression of a heat-shock protein 70 (Hsp70) on acid-shocked EPEC, and pretreatment with anti-Hsp70 eliminated the adhesion enhancement after acid stress. Acid shock also correlated with increased binding to sulfogalactosylceramide, a putative receptor for other pathogens after stress. CONCLUSIONS: Acid/bile-salt stress of EPEC significantly enhances adhesion to host cells, and a novel adhesin-receptor pair may play a role in the adhesion.

Acids↗

Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers.

The objective of the present investigation was to evaluate an oral 'drug delivery' approach, which involves co-administration of absorption enhancers (AEs). The representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drugs used in the study comprised of cefotaxime sodium and ceftazidime pentahydrate, whereas low permeable lipophilic (BCS Class IV) drugs include cyclosporin A and lovastatin. AEs from three different chemical classes, namely, medium chain fatty acids (sodium caprylate and caprate), cyclodextrins (beta-cyclodextrin, hydroxypropyl beta-cyclodextrin) and bile salts (sodium cholate and deoxycholate) were evaluated for absorption enhancement efficacy, mechanism of action and toxicity using in vitro everted intestinal sac model. These AEs were found to enhance intestinal permeability of drugs from 2- to 27-fold. Light microscopy studies of intestinal sac incubated with AEs for 120 min revealed morphological changes in absorptive mucosa and rank order of toxicity were cyclodextrins>bile salts congruent with medium chain fatty acids. Fluorescence polarization studies indicated that brush bordered membrane vesicles labeled with lipophilic (DPH, 12AS) and hydrophilic dyes (ANS), when treated with AEs exhibited concentration and time dependent decrease in fluorescence polarization. Total protein released in presence of AEs was more than control but considerably less than EDTA (0.58% w/v), which is known to cause toxic release of proteins from cell. Overall, AEs were found to significantly enhance drug permeability by decreasing lipid membrane fluidity and/or interacting with hydrophilic domains of membrane, and has the potential to improve oral delivery.

Animals↗

Bile salt/acid induction of DNA damage in bacterial cells: effect of taurine conjugation.

Bile salts and acids have been implicated in the etiology of colon cancer, possibly through their ability to cause DNA damage. Taurine-conjugated and nonconjugated forms of three bile salts and one bile acid were tested for DNA repair-inducing potential and for cellular toxicity in a recently developed Escherichia coli chromotest system. The taurine-conjugated forms of sodium deoxycholate and lithocholic acid had reduced ability to induce DNA repair. Also the taurine-conjugated form of lithocholic acid had a reduced lethal effect. These observations suggest that the biotransformation step, whereby bacteria in the intestine remove the taurine added to bile salts in the liver, may be significant in the etiology of colon cancer.

Bile Acids and Salts↗

Electron microscopic study of intestinal fat absorption in vitro from mixed micelles containing linolenic acid, monoolein, and bile salt.

Sacs and segments of everted hamster gut were incubated in vitro in solutions of mixed micelles (containing taurodeoxycholate, monoolein, and linolenic acid) for various periods and at different temperatures. The appearance of electron micrographs of the tissues was consistent with the hypothesis that the lipids were taken up in small particles (of micellar or molecular dimensions) by means of diffusion. There was no stimulation of pinocytosis or alteration in pinocytotic vesicles in the terminal web during uptake. In the deep cytoplasm the lipids accumulated to form large osmiophilic droplets of two kinds: (a) large, solitary droplets contained only by the matrix of the cytoplasm, without confining membranes; (b) small droplets occurring in clusters, without evidence of coalescence, within the granular and agranular endoplasmic reticulum. There was a progressive accumulation of the small droplets with time. Similar droplets appeared in extracellular spaces, including the lacteals, after prolonged incubations at 37 degrees C. The droplets in the endoplasmic reticulum appear to be the end product of lipid absorption and to be closely related to chylomicrons. These processes resemble those occurring during absorption of triglycerides in vivo and support the idea that this occurs predominantly through the formation of mixed micelles of the type employed in this study.

Animals↗

Bile salts of the West Indian manatee, Trichechus manatus latirostris: novel bile alcohol sulfates and absence of bile acids.

The bile salts present in gallbladder bile of the West Indian manatee, Trichechus manatus latirostris, an herbivorous marine mammal of the tropical and subtropical margins of the Atlantic Ocean, were found to consist of a mixture of bile alcohol sulfates. Bile acids, previously believed to be present in all mammals, were not detected. Using chromatography, mass spectrometry, and 1H- and 13C-nuclear magnetic resonance spectroscopy, the major bile alcohol was identified as 5 beta-cholestane-3 alpha,6 beta,7 alpha-25,26-pentol; that is, it had the nuclear structure of alpha-muricholic acid and the side chain structure of bufol. This compound has not been described previously and the trivial name "alpha-trichechol" is proposed. The second most abundant compound was 5 beta-cholestane-3 alpha,7 alpha,25,26-tetrol. Other bile alcohols were tentatively identified as 5 beta-cholestane-3 alpha,6 beta,7 beta,25,26-pentol (named beta-trichechol), 3 alpha,6 alpha,7 beta, 25-26-pentol (named omega-trichechol) and 5 beta-cholestane-3 alpha,6 beta,7 alpha,26-tetrol. The 1H and 13C NMR spectra of the four 6,7 epimers of 3,6,7 trihydroxy bile acids are described and discussed. All bile alcohols were present as ester sulfates, the sulfate group being tentatively assigned to the 26-hydroxy group. 12-Hydroxy compounds were not detected. The manatee is the first mammal found to lack bile acids, presumably because it lacks the enzymes required for oxidation of the 26-hydroxy group to a carboxylic acid. Trichechols, like other bile salts, are water-soluble end products of cholesterol metabolism; whether they also function as biological surfactants in promoting biliary cholesterol secretion or lipid digestion is unknown.

Animals↗

Enhancement of intestinal insulin absorption by bile salt-fatty acid mixed micelles in dogs.

The pharmacokinetics and pharmacodynamics of porcine zinc insulin following intravenous (iv), intrajejunal, and ileocolonic delivery were evaluated in dogs. The concentration-time profile of plasma immunoreactive insulin following iv injection could be best described by a two-compartment model with a mean distribution half-life of 1.1 min and a mean elimination half-life of 5.6 min. Maximum hypoglycemia occurred at 15 min after injection. Intrajejunal administration of 10 units/kg insulin in phosphate-buffered saline resulted in minimal insulin absorption or hypoglycemia. Incorporation of mixed micelles containing 30 mM sodium glycocholate and 40 mM linoleic acid significantly improved enteral insulin absorption. When delivered with mixed micelles, the mean absolute bioavailability of insulin was 1.8%. To study the effect of intestinal site on insulin uptake, the same formulation was delivered to the ileocolonic region. The mean absolute bioavailability of insulin absorbed from this site was 0.6%. Delivery of insulin to both sites caused significant hypoglycemia in all dogs. Insulin combined with mixed micelles is enterally absorbed in dogs; however, the bioavailability is much lower than that observed in similar studies with rats.

Animals↗