PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “bile acids”

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 19 recordsLinked to original sources
PubMed1977

[Correlation of malabsorption of bile acids, bile lipid composition and calculi].

The relation between malabsorption of bile acids, the bile lipid composition, and biliary stones was examined in 8 patients subjected to ileal resection (particularly for Crohn's disease), 6 with ileal bypass for morbid obesity, and 10 healthy controls. The 1-14C-cholylglycine breath test was employed to detect of the absorption and deconjugation of bile acids. Bile lipid composition was expressed according with Metzger's saturation index. Healthy subjects gave normal findings in all respects, whereas ileal resection was accompanied by malabsorption, increased deconjugation, and faecal loss of 14C. These changes, particularly malabsorption, were more evident after ileal bypass. Preoperative saturation values rose to more than 1 in all cases, especially after resection. Liver disease (steatosis and cirrhosis) 6 months after bypass, together with cholesterol lithiasis in 2/6 patients.

Adult↗
PubMed1977

Rabbit ileal mucosa exposed to fatty acids, bile acids, and other secretagogues. Scanning electron microscopic appearances.

Segments of rabbit ileum were examined by scanning electron microscopy (SEM) after exposure to various compounds known to stimulate fluid secretion in the small intestine. After perfusion with ricinoleate (castor oil) at a 10 mM concentration, striking changes were observed at villus tips and on the apicolateral surfaces of villi; erosions at tips were confirmed by light microscopy of the same pieces of tissue examined by SEM. The appearances after ricinoleate were reversed in part during perfusion with control buffer for 2 hr. Statistical comparisons between control perfused, treated, and reversal tissues showed that the "damage" produced by ricinoleate, and its reversal, was significant statistically. Tissues treated with other intestinal secretagogues, oleic acid (10 mM), deoxycholic acid (4 mM), cholic acid (4 mM), dioctyl sodium sulfosuccinate (6 mM), and cholera toxin (1 microgram/ml) also showed surface changes by SEM. Fluid secretion, produced by an osmotic agent (mannitol) was not associated with "damage." Changes in structure of the mucosal surface after exposure to intestinal secretagogues should be considered as one possible mechanism of impaired fluid transport.

Animals↗
PubMed1977

Evidence for renal control of urinary excretion of bile acids and bile acid sulphates in the cholestatic syndrome.

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gasliquid chromatography and gas-liquid chromoatography/mass spectrometry. 2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine. 3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant. 4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome. 5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3alpha, 7beta, 12alpha-trihydroxy-5beta-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney. 6. In bile only a small proportion of the bile acids was sulphated (range 2.1-4.6%) and in serum the degree of sulphation was very variable (9-50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33-72%). 7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.

Adult↗
PubMed1977

Effect of type and amount of dietary fat and 1,2-dimethylhydrazine on biliary bile acids, fecal bile acids, and neutral sterols in rats.

The effect of type (corn oil or lard) and quantity (5 or 20%) of dietary fat and 1,2-dimethylhydrazine (DMH) on the composition of biliary bile acids, fecal bile acids, and neutral sterols was studied in rats exposed to a given regimen for two generations prior to s.c. treatment with DMH for 20 weeks. Biliary excretion of total bile acids as well as cholic acid, beta-muricholic acid, ursodeoxycholic acid, and deoxycholic acid was higher in rats fed a diet containing 20% corn oil or lard than it was in rats fed diets containing 5% corn oil or lard. Treatment of animals with DMH produced an increase in biliary total bile acids, cholic acid, hyodeoxycholic acid, and deoxycholic acid irrespective of diets. High-fat (corn oil or lard at 20% level) intake was associated with an increased excretion of fecal neutral sterols and bile acids. The excretion of deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid was increased in rats fed high-fat diets. The source of fat had no major influence on the excretory pattern of cholesterol metabolites and bile acids. DMH-treated animals excreted higher levels of fecal coprostanol, coprostanone, deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid than did controls.

Animals↗
PubMed1978

Bile acids LVIII. Bile acids and colorectal cancer.

Significant correlations have been reported by epidemiologists between the mortality from colorectal cancer in various populations and the consumption of meat or lipids by these populations. These have directed considerable attention to possible relationships between diet and the occurrence of this neoplasm. We have carried out studies of the composition of bile from rats as influenced by diets of varying lipid content. Two cannulas were surgically implanted to form an externalized bile duct through which bile was drained from the common duct and returned to the duodenum. Small aliquots were analyzed for total bile acids by enzymatic assay and for individual bile acids by high-pressure liquid chromatography, gas chromatography and gas chromatography-mass spectometry. Animals consuming diets highest in lipid content provided bile with the greatest amounts of bile acids. The primary bile acids, taurocholic, taurochenodeoxychilic, and tauro alpha- and beta-muricholic acids made up more than 99% of the 3 alph-hydroxy bile acids and were found in approximate molar ratio of 2:1:1. Either complete drainage of bile without return to the duodenum, or biliary tract obstruction had pronounced influence on the rate of secretion of bile and its composition.

Animal Feed↗
PubMed1992

Liver-specific drug targeting by coupling to bile acids.

Bile acids are selectively taken up from portal blood into the liver by specific transport systems in the hepatocyte plasma membrane. Therefore, studies were performed to evaluate the potential of bile acids as shuttles to deliver drugs specifically to the liver. The alkylating cytostatic drug chlorambucil and the fluorescent prolyl-4-hydroxylase inhibitor 4-nitrobenzo-2-oxa-1,3-diazol-beta-Ala-Phe-5-oxaproline-Gly were covalently linked via an amide bond to 7 alpha, 12 alpha,-dihydroxy-3 beta- (omega-aminoalkoxy)-5-beta-cholan-24-oic acid. The chlorambucil-bile acid conjugates S 2521, S 2539, S 2567, and S 2576 inhibited Na(+)-dependent [3H]taurocholate uptake in a concentration-dependent manner both into isolated rat hepatocytes and rabbit ileal brush border membrane vesicles, whereas the parent drug chlorambucil showed no significant inhibitory effect. The chlorambucil-bile acid conjugates were able to prevent photoaffinity labeling of bile acid binding proteins in rat hepatocytes by the photolabile [3H]7,7-azo derivative of taurocholic acid indicating their bile acid character. The chlorambucil-bile acid conjugate S 2577 was able to alkylate proteins demonstrating the drug character conserved in the hybrid-molecules. Liver perfusion experiments revealed a secretion profile of the chlorambucil-bile acid conjugate S 2576 into bile very similar to taurocholate compared to chlorambucil which is predominantly excreted by the kidney. 4-Nitrobenzo-2-oxa-1,3-diazol-beta-Ala-Phe-5-oxaproline-Gly- t-butylester (S 4404), a fluorescent peptide inhibitor of prolyl-4-hydroxylase, was not transported in intact form from portal blood into bile in contrast to its bile acid conjugate S 3744; about 25% of the peptide-bile acid conjugate S 3744 was secreted in intact form into bile within 40 min compared with less than 4% of the parent oxaprolylpeptide S 4404. In conclusion, these studies reveal that modified bile acid molecules can be used as "Trojan horses" to deliver a drug molecule specifically into the liver and the biliary system. This offers important pharmacological options for the development of liver-specific drugs.

Affinity Labels↗
PubMed1989

Cholestasis of total parenteral nutrition: bile acid and bile lipid metabolism in parenterally nourished rats.

As food in the intestine "drives" the enterohepatic circulation and bile acids influence bile flow, we postulated that the cholestasis of total parenteral nutrition might be due to bile acid changes, and the cholelithiasis and biliary sludge of total parenteral nutrition to bile lipid changes. We therefore studied bile acid and bile lipid metabolism in the following groups of rats, with and without bile fistula: (a) nonfasted, orally fed controls, (b) orally fed controls fasted for 20 h, and (c) after 7 days of total parenteral nutrition. Biliary bile acid concentration (35.4 +/- 2.5 mM) and secretion (253 +/- 20.0 mumol/100 g body wt.24 h) increased significantly in the rats on TPN and the rats fasted for 20 h (38.8 +/- 2.5 and 243 +/- 23.4 mM, respectively) when compared with the orally fed controls (26.5 +/- 2.5 and 178 +/- 23.5 mM, respectively). Bile flow, however, was unchanged. Bile acid pool size (Eriksson washout technique) also increased from 43.4 +/- 3.0 mumol/100 g body wt in the controls to 50.5 +/- 4.8 in the group fasted for 20 h and 65.6 +/- 5.3 in the TPN group (p less than 0.05-0.01). Similar bile acid pool sizes (carcass extraction method) were found in the nonfistulated animals. Biliary cholesterol secretion and saturation were significantly less in the TPN rats than in the other two groups. Liver microscopy indicated only minimal fatty change, but serum bile acid and alkaline phosphatase levels were increased in the TPN group (p less than 0.05). Thus, during TPN bile acids stagnate within the enterohepatic circulation, increasing biliary bile acid concentration and secretion rates and expanding the pool size. However, the absence of an associated choleresis, together with abnormal liver function tests, suggest that alterations in bile acid metabolism cause a relative cholestasis in this model.

Animals↗
PubMed1990

Modulation of human colonic lamina propria lymphocyte proliferation. Effect of bile acids and oxidized fatty acids.

Bile acids were been implicated in several pathologic processes, such as secretory diarrhea, carcinogenesis, and immunomodulation of human peripheral blood lymphocytes. Nevertheless, their effect on the human gut immune system is not known. In this study we investigate the effect of several bile acids (cholate, deoxycholate, chenodeoxycholate) and 13-hydroperoxylinoleic acid (conc. 0.1-1000, microM) on human colonic lamina propria lymphocyte (LPL) DNA synthesis and cell proliferation. In addition, the effect of these bile acids on LPL ornithine decarboxylase activity was also determined. Significant dose-dependent inhibition of [3H]thymidine incorporation in Con A-stimulated LPL was observed. Parallel inhibition was seen on LPL cell proliferation. Furthermore, bile acids inhibited ornithine decarboxylase activity in Con A-stimulated LPL. These effects on cell proliferation were not due to the LPL cytolysis as viability and cell membrane integrity were not altered. Our results suggest that bile acid has an immunoregulatory function on the human mucosal immune system and may have a role during pathological states.

Adult↗
PubMed1991

Unchanged levels of keto bile acids in bile after cholecystectomy.

Cholecystectomy has been hypothesized to cause increased levels of potentially harmful secondary bile acids due to prolonged exposure of primary bile acids to intestinal bacteria. In the present study, we analyzed duodenal bile of the same patients before and after cholecystectomy for keto bile acids and hydroxy bile acids. The ratios of individual keto bile acids to their corresponding precursor hydroxy bile acids were not significantly different before and after cholecystectomy. Keto bile acids constituted 2.5 +/- 1.3 and 2.2 +/- 0.9 mol% of hydroxy bile acids in duodenal bile. 3 alpha-Hydroxy-12-oxo-5 beta-cholanoic acid derived from deoxycholic acid was the main keto bile acid in bile contributing 80 mol% to total keto bile acids. There was a strong positive correlation between 3 alpha-hydroxy-12-oxo-5 beta-cholanoic acid and its precursor deoxycholic acid in bile (r = 0.88; p less than 0.0005). Our findings prove that 7 weeks after cholecystectomy the percentage of keto bile acids in bile as compared to hydroxy bile acids is not increased.

Adult↗
PubMed1979

Preparation of [3beta-3H] labeled bile acids and bile alcohols.

[3beta-3H]-bile acids and bile alcohols may be useful for metabolic studies in man and animals because the 3-position is invulnerable to bacterial attack. A number of tritium labeled bile acids and bile alcohols were prepared by selective oxidation of the hydroxyl group at carbon-3 followed by reduction with NaBT4. In each case, the bile acids and bile alcohols epimeric at carbon-3 were resolved by analytical and preparative thin-layer chromatography and characterized by gasliquid chromatography. The average yield was 60--65% and specific activities of the final products were in the range of 7.4 x 10(7) dpm/mg.

Bile Acids and Salts↗
PubMed1990

Bile acid secretion, bile flow and biliary lipid secretion in humans.

The transport of bile acids through the hepatocyte and the effect of this flux of molecules on bile flow, biliary lipid secretion and bile acid biosynthesis are reviewed. Efficient hepatic clearance of bile acids involves several active systems and passive uptake. Formation of coenzyme A derivatives prevents reflux of lipophilic dihydroxy bile acids. Biotransformation of bile acids during hepatocyte transport involves both type I and type II biotransformations. The major type II biotransformation is reamidation of unconjugated bile acids, but sulfation and glucuronidation also occur. The only major type I biotransformation is oxidoreduction, which converts iso- or 3 oxo bile acids to the preferred 3 alpha-hydroxy form and 7 oxo bile acids to their corresponding 7 alpha-hydroxy derivatives. Secretion of bile acids into the canaliculus is concentrative and induces osmotic flow of plasma water and solutes across the paracellular junctions between the space of Disse and the canaliculus. Bile flow in man is characterized by its low volume and by a paucity of bile acid-independent flow when compared with that of other mammals. Bile acid secretion also induces biliary lipid secretion, but some lipid secretion appears to be bile acid independent. The lipid vesicles secreted in human bile have a much higher cholesterol/phospholipid ratio than those of other mammals. During flow down the biliary tree, vesicles are solubilized by bile acid micelles, and Ca++ ions are complexed by bile acid monomers and micelles. However, the biochemical mechanisms and factors regulating biliary lipid secretion in man are poorly understood.

Bile↗
PubMed1989

Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis.

We have compared the effect of ursodeoxycholic acid with placebo on the clinical state, blood liver chemistries and serum and urinary bile acids in four patients with primary biliary cirrhosis. All parameters were evaluated monthly, and bile acid composition was measured by capillary gas-liquid chromatography. At the time of admission, all patients showed intense pruritus, and their serum alkaline phosphatase, AST and ALT levels were elevated 4.3, 2.7 and 2.3 times over control values. Serum bile acids were elevated almost 38-fold with 2.5 times more cholic acid than chenodeoxycholic acid. Urinary bile acid output was elevated 28 times the control values, and 36% were 1 beta-hydroxycholic acid, 1 beta-hydroxydeoxycholic acid and hyocholic acid (3 alpha,6 alpha, 7 alpha-trihydroxy-5 beta-cholanoic acid). Three months of placebo administration did not significantly affect the clinical or biochemical presentations, and the serum and urinary bile acid composition did not change. In contrast, ursodeoxycholic acid feeding (12 to 15 mg per kg per day) for 6 months abolished pruritus in two and lessened itching in two subjects and reduced serum alkaline phosphatase, AST and ALT levels by 21, 35 and 47%, respectively. The mean values for the total serum bile acid concentrations in these patients declined 26% from the pretreatment value, but the proportion of ursodeoxycholic acid increased from 3 to 40% of the total bile acids; thus, total fasting serum endogenous bile acid levels decreased almost 50%. Similar changes were noted in the urinary bile acids, in which ursodeoxycholic acid became the major bile acid, and approximately 18% were hydroxylated at C-1, C-6 and C-21.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit.

Feedback regulation of derepressed hepatic bile acid biosynthesis was studied individually with glycocholic, glycodeoxycholic, and glycoursocholic acids by infusion into bile acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile acid pool (90% glycodeoxycholic acid, 10% glycocholic acid) within 24 hours and elicited maximal bile acid synthesis after about 72 hours, at which time glycocholic acid became the only biliary bile acid (greater than 98%). Replacement of the bile acid pool with glycocholic acid or glycodeoxycholic acid at a rate equivalent to the hepatic endogenous bile acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic acid, the 7 beta-hydroxy epimer of glycocholic acid, failed to suppress synthesis. Hepatic bile acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7 alpha-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic acid. Glycodeoxycholic acid infusion depressed cholesterol 7 alpha-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic acid infusion, were not affected by glycodeoxycholic acid infusion, but increased 19% and 43%, respectively, during glycoursocholic acid infusion. These results show that in rabbits the feedback regulation of hepatic bile acid synthesis depends on the hepatic flux of the normally present endogenous bile acids glycocholic acid and glycodeoxycholic acid but does not respond to the 7 beta-hydroxy glycoursocholic acid. Glycocholic acid inhibits both HMG-CoA reductase and cholesterol 7 alpha-hydroxylase while glycodeoxycholic acid affects primarily cholesterol 7 alpha-hydroxylase. Thus, the regulation of bile acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile acid synthesis.

Animals↗
PubMed1992

Lytic effects of mixed micelles of fatty acids and bile acids.

It has been hypothesized that bile acids and fatty acids promote colon cancer. A proposed mechanism is a lytic effect of these surfactants on colonic epithelium, resulting in a compensatory proliferation of colonic cells. To investigate the first step of this hypothesis, we studied the lytic activity of fatty acids and physiological mixtures of fatty acids and bile acids. Experiments were performed in both erythrocytes and cultured Caco-2 cells, a model system for intestinal epithelium. Fatty acids with a chain length of 10 C atoms or more were lytic, and the hemolytic activity increased in the order C10:0 less than C18:0 less than C16:0 less than C12:0 less than C14:0 much less than C18:1 approximately C18:2 but was not dependent on their critical micellar concentration. Addition of a sublytic, submicellar concentration of cholate resulted in the formation of highly lytic mixed micelles. Lytic activity of these mixed micelles was closely associated with their micellar aggregation as determined in parallel incubations using a fluorescent micellar probe. With use of identical concentrations of fatty acids and mixed micelles, lysis of erythrocytes was highly correlated (r greater than 0.95) with lysis of Caco-2 cells measured by either release of the apical membrane-marker alkaline phosphatase or the cytosolic marker lactate dehydrogenase. This indicates that the cytolytic activity of these surfactants is not cell-type dependent. Addition of bile acids in concentrations corresponding with the total bile acid concentration in human fecal water resulted in an increased lytic activity of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1989

Formation of delta 2- and delta 3-cholenoic acids from bile acid 3-sulfates by a human intestinal Fusobacterium strain.

We isolated two strains of an unnamed Fusobacterium species from human intestinal microflora, which stereospecifically transformed bile acid 3-sulfates into C-3-unsubstituted, ring A-unsaturated bile acids. Both 3 alpha- and 3 beta-sulfates of 5 beta-bile acids were metabolized to delta 3-5 beta-cholenoic acids; 3 beta-sulfates of 5 alpha-bile acids were converted into a mixture of delta 2-5 alpha-bile acids and 3 alpha-hydroxy-5 alpha-bile acids, whereas 3 alpha-sulfates of 5 alpha-bile acids were left intact. Unsulfated bile acids were not transformed into unsaturated derivatives. These strains differ from previously isolated intestinal bacteria, which desulfated bile acid sulfates without further transformation.

Bile Acids and Salts↗
PubMed1975

Effect of primary bile acid ingestion on bile acid metabolism and biliary lipid secretion in gallstone patients.

Bile acid kinetics were measured by isotope dilution, and hourly outputs of bile acid, cholesterol, and phospholipid were quantified by duodenal perfusion over 24 hr including three liquid meals and an overnight fast in 6 gallstone patients during a pretreatment period and two randomized treatment periods with chenodeoxycholic (chenic) acid or cholic acid. During chenic acid ingestion, bile contained predominantly chenyl conjugates. During cholic acid ingestion, bile was composed of about equal amounts of cholyl and deoxycholyl conjugates; chenyl conjugates decreased markedly due in part to a 50% decrease in chenic acid synthesis. Total bile acid pool size doubled in half the patients receiving either bile acid and was not different during treatment with chenic or cholic acid. Compared to cholic acid, chenic acid caused decreased cholesterol output with no difference in bile acid or phospholipid output. Therefore, bile unsaturated with cholesterol entered the duodenum for more hours per day during chenic acid ingestion than during the cholic or pretreatment periods. There was no relationship among bile acid pool size, bile acid output, and hours per day of supersaturated bile; there was an inverse relationship between total pool size and recycling frequency such that bile acid output remained stable over a wide range of pool sizes. Fasting-state gallbladder bile was supersaturated during the cholic and pretreatment periods, but became unsaturated during chenic acid ingestion. However, hours per day of supersaturated bile could not be reliably predicted from the degree of saturation of fasting-state gallbladder bile (r = 0.62). The efficacy of chenic acid and the lack of efficacy of cholic acid for gallstone dissolution appear related to their different specific effects on biliary cholesterol secretion and not to any effect on bile acid and phospholipid secretion or bile acid pool size.

Bile↗
PubMed1975

An enzymic method for the determination of the glycine/taurine ratio of conjugated bile acids in bile.

A method is described in which the ratio of the glycine- to taurine-conjugated bile acids (G/T ratio) in bile is determined. After pretreatment of the bile for removal of the lipids, the bile acids are deconjugated enzymically with choloylglycine hydrolase (EC 3.5.1.24). The amino acids taurine and glycine are liberated in this way, after appropriate isolation, taurine and/or glycine are then determined with ninhydrin, enabling the establishment of the G/T ratio. A nearly complete hydrolysis was obtained for 6 conjugated bile acids, while the recovery of these acids when added to hog or ox bile was quantitative. The mean G/T ratio for hog bile, ox bile and human B-bile was 6.3, 2.5 and 2.0, respectively. The amount of total, free and conjugated bile acids can be determined by this method, combined with the 3alpha-hydroxysteroid dehydrogenase technique for bile acid determination described by Iwata and Yamasaki [1]. A high G/T ratio was observed in 3 cases of Crohn's disease in the small bowel, but the extent of deconjugation in B-bile was lower than in duodenal fluid. The determination of the G/T ratio can be complementary to our knowledge of the metabolism of bile salts in certain gastro-intestinal disorders.

Amidohydrolases↗