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PubMed1994

Changes in bile acid composition of serum and gallbladder bile in bile duct ligated dogs.

Biliary obstruction was produced by surgical ligation of the common bile duct to observe alterations in serum bile acid composition. The percent composition of serum bile acids was found to change with time. Taurocholic acid increased on day 3 and accounted for more than 90% of the total bile acids in all dogs, however it decreased after day 7. The percentage of taurochenodeoxycholic acid (TCDC) and taurodeoxycholic acid (TDC) decreased to 4.2-6.0% and 0.2-0.7% on day 3, respectively. However, the percentage of TCDC increased after day 7 in all dogs and reached greater than 20% on day 14 in 2 dogs, whereas the percent TDC after bile duct ligation remained low in all dogs. Glycolithocholic acid, which was not identified in normal dog sera, was detected on day 3 and remained throughout the study in all dogs. Bile acid composition of gallbladder bile sampled on day 35 was similar to the serum bile acid composition on the same day. This indicates that the bile acids refluxed into the circulation in these dogs. In the present study, total cholic acid to chenodeoxycholic acid (C:CDC) ratio increased to 15.5-22.3 at three days post bile duct ligation and after the day 14, the C:CDC ratio decreased to its pre-ligation value or below. In contrast, the glycine conjugated to taurine conjugated bile acids (G:T) ratio did not change. Therefore, at this time, the G:T ratio would not be usable as an indicator of liver disease in dogs while it may be possible to use the C:CDC ratio.

Animals↗
PubMed2000

Dietary cholesterol induces changes in molecular species of hepatic microsomal phosphatidylcholine.

After 21 days on a diet containing 1 g% cholesterol and 0.5 g% cholic acid, rats had an increased content of cholesterol in liver microsomal lipids. In liver, both cholesterol content and delta9 desaturase activity increased, whereas delta6 and delta5 desaturase activities decreased. These changes correlated with increases in oleic, palmitoleic, and linoleic acids and decreases in arachidonic and docosahexenoic acids in total microsomal lipids. Similar fatty acid changes were found in phosphatidylcholine (PC), the principal lipid of the microsomal membrane. In PC the predominant molecular fatty acid species (67% of the total) in the control rats were 18:0/20:4, 16:0/20:4, and 16:0/18:2; and they mainly determined the contribution of PC to the biophysical and biochemical properties of the phospholipid bilayer. The cholesterol diet decreased specifically the 18:0/20:4 species, and to a lesser extent, 16:0/20:4 and 18:0/22:6. The 18:1-containing species, especially 18:1/18:2 and less so 16:0/18:1 and 18:1/20:4, were increased. A new 18:1/18:1 species appeared. The independent effects of the presence of cholesterol and change of the fatty acid composition of the phospholipid bilayer of liver microsomes on the packing were studied by fluorescence methods using 6-lauroyl-2,4-dimethylaminonaphthalene, 1,6-diphenyl-1,3,5-hexatriene and 1-(4-trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene, which test different parameters and depths of the bilayer. Data showed that the increase of cholesterol in the membrane, and not the change of the fatty acid composition of phospholipids, was the main determinant of the increased bulk packing of the bilayer. The increase of fluid oleic- and linoleic-containing species almost compensated for the drop in 20:4- and 22:6-containing molecules. But the most important effect was that the general drop in essential n-6 and n-3 polyunsaturated fatty acids meant that this endogenous source for the needs of the animal decreased.

Animals↗
PubMed1977

Sterol and bile acid metabolism during development. 1. Studies on the gallbladder and intestinal bile acids of newborn and fetal rabbit.

Bile acid composition and content in the intestine and gallbladder of newborn and fetal rabbits were investigated. Unlike the circumstances in adult rabbits, the bile acids were conjugated with both taurine and glycine. The major bile acids of the fetus and newborn rabbit were cholic acid, chenodeoxycholic acid, and deoxycholic acid. This is different from the known bile acid composition of adult rabbits, in which deoxycholic acid is the major bile acid (greater than 80%). The proportion of chenodeoxycholic acid was higher in the fetal than in the newborn tissues. The total bile acid pool in the newborn was higher than in the fetus. In the fetus, large proportions of bile acids (60.9%) were associated with the gallbladder fraction, whereas in the newborn the bulk of the bile acids were found with the intestinal fraction (64.4%).

Animals↗
PubMed2003

Inhibitory effect of the small heterodimer partner on hepatocyte nuclear factor-4 mediates bile acid-induced repression of the human angiotensinogen gene.

Bile acids function as transcriptional regulators for the genes important in bile acid synthesis and cholesterol homeostasis. In this study, we identified angiotensinogen (ANG), the precursor of vasoactive octapeptide angiotensin II, as a novel target gene of bile acids. In human ANG transgenic mice, administration of cholic acid resulted in the down-regulation of human ANG gene expression in the liver. ANG gene expression in HepG2 cells was also repressed by chenodeoxycholic acid. Because the expression of small heterodimer partner (SHP) mRNA was induced by chenodeoxycholic acid in HepG2 cells, we analyzed the effects of SHP on the human ANG promoter. Promoter mutation analysis demonstrated that SHP repressed human ANG promoter activity through the element, which has been previously determined as a binding site for hepatocyte nuclear factor-4 (HNF-4). SHP repressed human ANG promoter activity only when the HNF-4 expression vector was cotransfected in HeLa cells. Furthermore, we found that SHP bound to the HNF-4 N-terminal region including the DNA-binding domain and activation function-1 and that SHP prevented HNF-4 from binding to the human ANG promoter. These results suggest that bile acids negatively regulate the human ANG gene through the inhibitory effect of SHP on HNF-4.

Angiotensinogen↗
PubMed1977

Fetomaternal relationships of serum bile acids in uncomplicated pregnancy.

Simultaneous umbilical cord arterial, cord venous, and maternal peripheral venous blood samples were collected in labour in twenty-five uncomplicated human pregnancies at term, and the concentrations of serum bile acids were determined by a gas chromatographic method. Cholic acid (C) predominated in the maternal and chenodeoxycholic acid (CD) in the fetal serum samples; the mean ratios of C to CD were 1.50 and 0.92, respectively. Mean concentrations of C and CD were significantly higher in the cord venous (1.27 and 1.55 mumol/l, respectively) than in the maternal venous (0.81 and 0.63 mumol/l, respectively) serum samples. Paired cord arteriovenous comparisons showed that concentrations of C and CD were slightly higher in the cord arterial as compared with the cord venous serum. These results indicate that the placenta is capable to maintain a considerable concentration difference of bile salt between the fetal and maternal compartment. It seems on the basis of cord arteriovenous differences that C and CD are to some extent eliminated from the fetal to the maternal compartment by transplacental passage.

Bile Acids and Salts↗
PubMed1976

The use of bile salts to improve absorption of tallow in chicks, one to three weeks of age.

Apparent fat absorption was 39.6 and 68.2% in chicks 4-7 and 14-19 days of age, respectively, fed purified-type diets with 8.2% tallow (TLW). Cholic acid (C.A.), chenodesoxycholic acid (Ch.A.) and taurocholate, sodium salt (T.A.) at .025 and .05% increased significantly the apparent absorption of fat by 8.4 percentage units in chicks 4-7 days of age, and as much as 10 percentage units in chicks 14-19 days of age. No significant increase in metabolized energy of diets was detected. C.A. was fed to S.C.W.L. hens at graded levels up to .2% in corn-soy diets containing either 4 or 8% TLW or hydrogenated soybean oil. No improvement in fat absorption or M.E. was detected in these hens which absorbed 86-89% of the fat. The data indicate that bile salts appear to be effective in improving the absorption of saturated-type fats only in young chicks whose absorptive mechanism for fat is not fully developed.

Age Factors↗
PubMed1989

Effect of dietary fiber from banana (Musa paradisiaca) on metabolism of carbohydrates in rats fed cholesterol free diet.

Effect of feeding isolated dietary fiber from M. paradisiaca on the metabolism of carbohydrates in the liver has been studied. Fiber fed rats showed significantly lower levels of fasting blood glucose and higher concentration of liver glycogen. Activity of glycogen phosphorylase, glucose-1-phosphate, uridyl transferase and glycogen synthase was significantly higher while phosphoglucomutase activity showed lower activity. Activity of some glycolytic enzymes, viz. hexokinase and pyruvic kinase was lower. Glucose-6-phosphatase showed higher activity while fructose 1-6 diphosphatase activity was not affected. Glucose-6-phosphate dehydrogenase on the other hand showed higher activity. The changes in these enzyme activities have been attributed due to the effect of higher concentration of bile acids produced in the liver as a result of feeding fiber. Evidence for this has been obtained by studying the in vitro effect of cholic acid and chenodeoxy cholic acid.

Animals↗
PubMed1982

Tetrahydroxylated bile acids in healthy human newborns.

Urine was collected in four healthy infants, born after 35-39 weeks of gestation. The collections were made for 24 h starting immediately after birth. Bile acids were extracted, separated into conjugate groups, solvolysed, hydrolysed and quantified by gas-liquid chromatography as methyl ester trimethylsilyl ether derivatives. Identification was made by gas-liquid chromatography-mass spectrometry. Cholic acid was the predominating primary bile acid. Non-sulphated tetrahydroxylated bile acids, tentatively identified as 1,3,7,12- and 3,6,7,12-tetrahydroxycholanoic acids, were present in almost the same amounts as cholic acid. A previously unknown tetrahydroxylated cholanoic acid, which might be 2-hydroxylated hyocholic acid, was found in all infants in similar amounts. 3 beta-Hydroxy-5-cholenoic acid was present in the sulphate fraction in the urine from all infants. Lithocholic acid was not found. Small amounts of allo and 6-hydroxylated bile acids were mainly found in the sulphate fraction. Bile acids hydroxylated in the 1-position were found predominantly in the taurine fraction.

Adult↗
PubMedDate not supplied

[Change in the exocrine function of the liver after cholecystectomy under the influence of diet therapy].

In patients with sustained cholecystectomy the content of the basic bile components (cholesterol, cholic acid, total phosphorus) was measured. The cholate-cholesterol coefficient, enabling it to a certain degree to evaluate the lithogeneity of the bile, was calculated. The cholesterol concentration in the serum and bile was contrasted. A total of 104 patients were examined at different post-operative periodss and it was found that in 70 per cent of them the bile was not oversaturated with cholesterol. Two variants of the No. 5 diet were used--the sparing and fatty, differing in the amount of fat and carbohydrates. Under the effect of the No. 5 sparing diet a reduced serum cholesterol concentration was noted along with a noticeable rise of the cholic acid content in the bile with a not too brusque rise of the cholesterol level therein, which led to an increase of the cholate-cholesterol coefficient. Against the background of the treatment with a No. 5 fat diet in evidence was a diminution of the serum cholesterol content, a clearcut fall in the cholesteroland cholic acid concentration in the bile with a continuing fairly high cholate-chole sterol coefficient.

Adult↗
PubMed1976

Fecal steroids in diarrhea. I. Acute shigellosis.

Fecal bile acid and neutral sterol patterns of five healthy adult male volunteers, who were challenged by a virulent Shigella flexneri 2a (M42-43) strain and developed dysentery were studied. It was observed that cholic acid was increased from 1.9 +/- 0.4% of total bile acid in the feces before infection to 14.5 +/- 2.1% during diarrhea (P less than 0.001). Chenodeoxycholic acid also was increased from 3.2 +/- 0.7 to 8.7 +/- 3.2% in diarrhea but the difference was not significant statistically. Deoxycholic and lithocholic acids constituted 34.1 +/- 4.1 and 40.5 +/- 2.8%, respectively, of total bile acid in the normal controls as compared to 13.9 +/- 2.5 and 24.8 +/- 2.5% for the same subjects during diarrhea (P less than 0.005). Total excretion of bile acids, expressed as mg/kg of body weight per day, were higher in diarrhea (5.4 +/- 1.0) than that in controls (4,2 +/- 1.0) but the difference was not statistically significant. In the neutral sterol fraction, unmodified cholesterol was increased during diarrhea (86.2 +/- 8.7 versus 25.0 +/- 4.8% of total cholesterol metabolites in controls, P less than 0.001). Coprostanol was decreased in shigellosis (12.2 +/- 8.2 versus 65.8 +/- 4.7% in controls, P less than 0.001). Epicoprostanol, coprostanone, and unidentified cholesterol metabolites also were reduced in shigellosis. The effect of diarrhea on the plant sterols was not as consistent. However, unidentified plant sterols were reduced significantly in shigellosis stools. Total excretion of cholesterol metabolites and plant sterols, when expressed as mg/kg of body weight per day, were 6.8 +/- 1.7 and 0.6 +/- 0.2), respectively, in Shigellosis. These values were not significantly different from the corresponding values for controls (10.3 +/- 3.0 and 0.8 +/- 0.2). One subject's stool samples were studied during infection for the sequence of bile acid alteration. A progressive reduction of bacterial activity upon fecal steroids was evident following the initial diarrheal episode. The production of coprostanol was correlated with 7 alpha-dehydroxylation of cholic acid (r = 0.937, P less than 0.001) and chenodeoxycholic acid (r = 0.755, P less than 0.01).

Acute Disease↗
PubMed1988

Effect of periodic long-term ethanol administration on biliary bile acids and bile secretion in the rat.

Hepatic bile flow and its bile acid composition were determined in a group of 23 rats receiving 20% (W/v) ethanol by daily intubations 5 times a week over a 10-12 week period and in a control group of 23 rats. The aim was to elucidate the well known role of alcohol in pancreatitis. Chronic ethanol administration resulted in a significant increase in 2-h bile production and bile secretion rates. Molar concentrations of total and individual bile acids were determined by the hydroxysteroid dehydrogenase method after thin layer separation. No significant differences in molar concentrations of total or separate bile acid were observed. Special attention was paid to free bile acids. A spot with a Rf value corresponding to cholic acid was found in 10 rats in each group. This was examined by mass spectrometry using direct inlet technique, but no free cholic acid could be identified. Thus it seems that the changes in the amounts of bile acids are not decisive for the origin of acute alcoholic pancreatitis but that increased bile flow caused by chronic alcohol ingestion may favour reflux of bile into the pancreas, resulting in pancreatitis.

Animals↗
PubMed1988

Defective bile acid amidation: predicted features of a new inborn error of metabolism.

Biochemical and clinical features are predicted for an as yet unreported inborn error of metabolism, in which bile acids cannot be conjugated with glycine or taurine. Unconjugated cholic acid will be secreted into bile, be absorbed from the intestine, and become the predominant bile acid in bile and plasma. Other bile acids will be esterified with glucuronate and secreted into bile, but undergo little enterohepatic circulation. Cholestasis will not be present; the bile acid pool will be diminished and lipid absorption, especially that of fat-soluble vitamins, will be impaired. A secretory diarrhoea may occur, caused by increased bile acid concentrations in the colon. Awareness of this possible syndrome should aid in its identification; oral administration of bile acids conjugated with glycine or taurine should correct the metabolic and clinical abnormalities.

Bile Acids and Salts↗
PubMed1997

Bile acid concentrations in serum and duodenal aspirates of healthy preterm infants: effects of gestational and postnatal age.

In 41 healthy human-milk-fed preterm infants the preprandial total bile acid (BA) concentrations in serum and duodenal juice were simultaneous measured during the first 60 days of life. The infants were subdivided into four groups according to their gestational age: 6 infants with a gestational age of 27 and 28 weeks, 7 infants with a gestational age of 29 and 30 weeks, 21 infants with a gestational age of 31 and 32 weeks and 7 infants with a gestational age of 33 and 34 weeks. The BA levels were enzymatically determined using 3-alpha-hydroxysteroid dehydrogenase. In the duodenal juice, cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid and lithocholic acid were separately quantified by thin-layer chromatography. During the first month of life, the serum BA concentrations increased significantly with postnatal age (p < 0.01) but remained nearly constant during the second month of life. In the duodenal aspirates, the BA concentrations increased continuously up to the end of the observations period (p < 0.001). In the duodenal aspirates, the CA/CDCA ratio was high immediately after birth and decreased significantly with increasing postnatal age (p < 0.001). During the first weeks of life, the BA levels were preferentially conjugated with taurine, but in spite of the taurine-rich diet during the whole observation period the taurine/glycine ratio decreased with postnatal age (p < 0.001). In all samples of duodenal juice, the sum of primary BA was > 98% of total 3-alpha-hydroxy-BA. These data indicate that the establishment of an intestinal microbial flora necessary for intestinal BA transformation and the development of the enterohepatic BA circulation lasts some months of postnatal life. The serum BA concentration reflects hepatic synthesis, intestinal absorption, renal excretion and hepatocellular transport into bile in a very complex way which may limit the diagnostic value of serum BA during this time. Additionally, a duodenal BA concentration below 4 mmol/l, as found in this study during the first 2 weeks of life, may be of clinical importance due to its possible effects on fat absorption.

Aging↗
PubMed2002

Binding of free bile acids by cells of yogurt starter culture bacteria.

Several strains of Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus, which produced exocellular polysaccharides (EPS), varied in the amount produced. The streptococci tended to produce the most EPS per milliliter of culture; however, when compared on the basis of amounts per 10(7) cfu, the lactobacilli produced the most. Lactobacillus delbrueckii ssp. bulgaricus strains Lb-18 and Lb-10442 and S. thermophilus St-143 produced significantly larger amounts per 107 cfu than did other strains tested. These three cultures plus two strains of the streptococci that produced the greatest amounts of EPS per ml of culture were tested for the ability to bind bile acids from laboratory media. The two cultures of L. delbrueckii ssp. bulgaricus (Lb-18 and Lb-10442) bound significantly higher amounts of cholic acid than did the three strains of streptococci. These two cultures of lactobacilli bound up to 15.3% of the cholic acid present in laboratory media, up to 452 microg/mg of EPS and 2.9 microg/10(7) cfu. None of the cultures tested in this study were able to bind the conjugated bile acid, glycocholic acid.

Cholic Acid↗
PubMed1988

Effect of 7-methylated bile acids and bile alcohols on cholesterol metabolism in hamsters.

The effect of 7-methyl substituted bile acid and bile alcohol analogues on cholesterol metabolism was studied in the hamster. Animals were fed chow plus 0.1% cholesterol supplemented with 0.1% of one of the following steroids: chenodeoxycholic acid, 7-methyl-chenodeoxycholic acid, 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 25-triol, cholic acid, 7-methyl-cholic acid, or 7 beta-methyl-24-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,25-tetrol. Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and beta-sitosterol. Of the six compounds studied, chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid decreased intestinal cholesterol absorption (17% and 31% decrease, respectively). Only 7-methyl-chenodeoxycholic acid decreased serum cholesterol concentration (29% decrease), but there were no analogous changes of liver and biliary cholesterol concentration and cholesterol saturation of bile. Total fecal neutral sterol excretion was increased in the groups fed chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid. In addition, the production of coprostanol was increased in both groups. These data suggest that 7-methyl-chenodeoxycholic acid resembles chenodeoxycholic acid in its effect on cholesterol metabolism and may be a potential candidate for further studies of its gallstone-dissolving properties.

Animals↗
PubMedDate not supplied

The formation of deoxycholic acid in patients with type II and IV hyperlipoproteinaemia.

The formation of deoxycholic acid (D) was studied in 8 patients with Type II hyperlipoproteinaemia and in 6 with Type IV hyperlipoproteinaemia, using orally administered [2.4--3H]cholic acid and [24--14C]deoxycholic acid. The diet was standardized and of natural type. The mean values for fractional turnover, pool size and D synthesis in the patients with Type II pattern were 0.23 days-1, 331 mg and 75 mg/day, respectively; in Type IV they were 0.39 days-1, 587 mg and 191 mg/day. Compared with a group of healthy subjects, the pool size and formation of D were normal in Type IV, but significantly reduced in Type II. The mean conversion of cholic acid into the circulating pool of D was calculated to be 37% in Type II, and 38% in Type IV patients. Both these values are within normal limits.

Adult↗
PubMed1982

Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum.

This investigation was undertaken in order to (a) characterize the postprandial inflow of individual bile acids to the liver and (b) determine if peripheral venous bile acid levels always adequately reflect the portal venous concentration, or if saturation of hepatic bile acid uptake can occur under physiological conditions. In five patients with uncomplicated cholesterol gallstone disease, the umbilical cord was cannulated during cholecystectomy, and a catheter was left in the left portal branch for 5 to 7 d. The serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid in portal venous and systemic circulation were then determined at intervals of 15 to 30 min before and after a standardized meal. A highly accurate and specific gas chromatographic/mass spectrometric technique was used. The sum of the fasting concentrations of the three bile acids averaged 14.04+/-4.13 mumol/liter in portal venous serum, and 2.44+/-0.31 mumol/liter in peripheral venous serum. The estimated hepatic fractional uptake of cholic acid was approximately 90%, and those of chenodeoxycholic acid and deoxycholic acid were 70-80%. This resulted in an enrichment of systemic bile acids in the dihydroxy bile acid species. In response to a standardized meal, portal venous bile acid concentrations increased two- to sixfold, with a peak seen 15-60 min after the meal. The maximum postprandial portal venous bile acid concentration averaged 43.04+/-6.12 mumol/liter, and the corresponding concentration in peripheral serum was 5.22+/-0.74 mumol/liter. The estimated fractional uptakes of the individual bile acids were not affected by the increased inflow to the liver. The peripheral venous concentrations of individual as well as total bile acids were well correlated with those in portal venous serum. The results (a) give a quantitation of postprandial bile acid inflow to the liver and (b) indicate that the hepatic uptake system for bile acids in healthy man cannot be saturated during maximal inflow of endogenous bile acids. Measurement of peripheral serum bile acids can thus give important information on the status of the enterohepatic circulation.

Aged↗