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PubMed1997

Cholesterol 7alpha-hydroxylase influences the expression of hepatic apoA-I in two inbred mouse strains displaying different susceptibilities to atherosclerosis and in hepatoma cells.

C57BL/6 mice are susceptible to diet-induced atherosclerosis, whereas BALB/c mice are resistant. The susceptibility of C57BL/6 mice has been linked to decreased plasma HDL cholesterol in response to a diet containing fat, cholesterol, and cholic acid. Feeding C57BL/6 mice a diet consisting of fat and cholesterol, but no cholic acid, increased plasma high density lipoprotein (HDL) cholesterol. The increase in HDL was associated with increases in both plasma apolipoprotein (apo)A-I and hepatic apoA-I mRNA. Supplementation of the cholesterol-rich diet with cholic acid inhibited the stimulatory effect of cholesterol on hepatic apoA-I mRNA expression, resulting in similar hepatic apoA-I mRNA levels compared to chow-fed mice. Atherosclerosis-resistant BALB/c mice were also resistant to diet-induced changes in plasma HDL, apoA-I, and hepatic apoA-I mRNA levels. Previous studies showed that the diets changed both the activity and mRNA encoding the liver specific enzyme 7alpha-hydroxylase (1993.J. Lipid Res. 34: 923-931). In both strains of mice, hepatic expression of apoA-I and 7alpha-hydroxylase mRNA varied in parallel. Whereas susceptible C57BL/6 mice also showed a significant correlation between HDL cholesterol and expression of 7alpha-hydroxylase, no such correlation was observed in BALB/c mice, suggesting that genetic differences in HDL metabolism, not hepatic apoA-I synthesis, are responsible for the strain specific differences in plasma HDL levels. The finding that lecithin: cholesterol acyltransferase (LCAT) activity was significantly decreased in C57BL/6 mice, but not in BALB/ c mice fed the atherogenic diet, further supports this conclusion. Additional studies show that McArdle hepatoma cells stably expressing plasmid-derived rat 7alpha-hydroxylase recapitulated the parallel linear relationship between 7alpha-hydroxylase and apoA-I mRNA expression observed in both strains of mice. These data link hepatic apoA-I mRNA expression to hepatic cholesterol/bile acid metabolism.

Animals↗

PubMed1978

Diurnal serum levels of primary conjugated bile acids. Assessment by specific radioimmunoassays for conjugates of cholic and chenodeoxycholic acid.

The serum levels of conjugates of chenodeoxycholic acid (chenyl conjugates) and of cholic acid (cholyl conjugates) were determined by specific radioimmunoassays during a 24-hour period, which included three liquid meals and an overnight fast, in five healthy volunteers, five patients with previous cholecystectomy, five patients with documented bile acid malabsorption because of ileal resection, and four pregnant women. In healthy subjects, fasting-state levels of chenyl conjugates, when compared with those of cholyl conjugates, were higher; postprandially, levels of chenyl conjugates rose to a peak sooner (30 minutes vs 60 minutes) and to higher levels (5.2 +/- 1.3 muM vs 2.0 +/- 0.5 muM, M +/- SE). In cholecystectomised patients, the integrated areas under the curve for both bile acids were similar to those of the healthy controls, but postprandial peaks were less marked. In patients with bile acid malabsorption, postprandial rises of chenyl conjugates were lower but remained relatively constant throughout the day, whereas cholyl conjugate levels diminished progressively with each successive meal, consistant with depletion of the cholyl, but not the chenyl, pool. In three of four pregnant women, the postprandial rise of chenyl conjugates was disproportionately less compared with that of healthy controls. These results confirm the dynamic complexity of serum bile acid levels in man and indicate that the major circulating primary bile acids are chenyl conjugates. They support previous proposals that jejunal absorption of chenyl conjugates is important in the normal enterohepatic circulation of bile acids; and they suggest an abnormality in the enterohepatic circulation in pregnancy.

Chenodeoxycholic Acid↗

PubMed1983

Comparative effects of ursodeoxycholic acid and chenodeoxycholic acid on bile acid kinetics and biliary lipid secretion in humans. Evidence for different modes of action on bile acid synthesis.

The effects of ursodeoxycholic acid on biliary lipid secretion and bile acid kinetics were determined in 12 men. For comparison, eight of the subjects were also treated with chenodeoxycholic acid using a crossover study design. The daily dose of each bile acid was 15 mg/kg body wt; each treatment period lasted for 5-6 wk. Kinetics of cholic acid and chenodeoxycholic acid, hepatic secretion rates of biliary lipids, and lipid composition of concentrated fasting duodenal bile were determined before and at the end of each treatment period. The synthesis rates of cholic acid and chenodeoxycholic acid were increased by approximately 80% and 40%, respectively, during treatment with ursodeoxycholic acid. The fractional catabolic rates of the two bile acids were increased by approximately 50%, whereas the pool sizes remained unchanged. Under similar conditions, administration of chenodeoxycholic acid reduced the pool size as well as the synthesis rate of cholic acid by approximately 70%. Ursodeoxycholic acid reduced the hepatic secretion of cholesterol to a higher extent (approximately 50%) than did chenodeoxycholic acid (approximately 30%). The secretion rates of bile acids and phospholipids remained essentially unchanged during the two treatment periods. Fasting duodenal (gallbladder) bile was unsaturated with cholesterol during both regimens. It is concluded that the two bile acids exert different effects on bile acid metabolism. The enhanced conversion of cholesterol to bile acids observed during ursodeoxycholic acid treatment may at least partly explain why ursodeoxycholic acid can reduce the biliary output of cholesterol without suppressing hepatic cholesterol synthesis.

Bile↗

PubMed1989

Bile acid synthesis in cell culture.

Confluent cultures of Hep G2 cells were found to synthesize chenodeoxycholic and cholic acids continually. Chenodeoxycholic acid was synthesized at the rate of 58 +/- 8.6 micrograms/96 h, a rate more than 7-fold greater than that for cholic acid. Addition of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol but not the -3 alpha, 7 alpha-diol was followed by an increase in cholic acid synthesis, thus indicating a relatively low 12 alpha-hydroxylase activity. Endogenous synthesis of monohydroxy bile acid ester sulfates was found, with maximum rates of 135 and 74 micrograms/96 h for lithocholic and 3 alpha-hydroxy-5-cholenoic acids, respectively. Incubation of Hep G2 cells in medium containing 25% D2O permitted a comparison of the precursor/product relationship of cholesterol with 3 beta-hydroxy-5-cholenoic acid. The pattern of incorporation of deuterium was in accordance with that expected, thus allowing the conclusion that this monohydroxy bile acid is derived from cholesterol and should be considered together with chenodeoxycholic and cholic acids as a primary bile acid.

Bile Acids and Salts↗

PubMed1993

Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy.

Serum bile acid levels and distributions were studied every 6 mo in patients with primary biliary cirrhosis who were randomly assigned to receive ursodeoxycholic acid (13 to 15 mg/kg/day) (n = 73) or a placebo (n = 73) over a 2-yr period. In the ursodeoxycholic acid group, ursodeoxycholic acid was the predominant serum bile acid at 6 mo and throughout the 2-yr treatment period. The total concentration of endogenous bile acids decreased with a reduction in cholic acid (in the ursodeoxycholic acid group and the placebo group, respectively [mean +/- S.E.]: 13.0 +/- 2.2 and 12.6 +/- 2.5 mumol/L at entry vs. 3.5 +/- 0.6 and 9.0 +/- 2.2 mumol/L at 2 yr; p < 0.002), chenodeoxycholic acid (in the ursodeoxycholic acid group and the placebo group, respectively: 12.1 +/- 1.7 and 12.7 +/- 2.3 mumol/L at entry vs. 5.8 +/- 0.8 and 10.7 +/- 2.2 mumol/L at 2 yr; p < 0.02) and 3 beta-hydroxy-delta 5-cholenoic acid. The concentration of deoxycholic acid did not change, whereas that of lithocholic acid increased significantly (in the ursodeoxycholic acid group and the placebo group, respectively: 0.63 +/- 0.06 and 0.81 +/- 0.12 mumol/L at entry vs. 1.26 +/- 0.12 and 0.90 +/- 0.15 mumol/L at 2 yr; p < 0.001). These changes were independent of the histological stage of the disease. Thus during ursodeoxycholic acid administration the liver was exposed to a lower level of endogenous bile acids and to an increased concentration of ursodeoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗

PubMed1996

Effects of beta-lactam antibiotics on intestinal microflora and bile acid metabolism in rats.

Wistar male rats were treated for six days with broad spectrum beta-lactam antibiotics, latamoxef, and cefotaxime. On the seventh day, the number of fecal anaerobic microbes decreased, total fecal bile acids decreased, and bile acid pools increased. Secondary bile acids such as beta-hyocholic, hyodeoxycholic, lithocholic, and deoxycholic acids decreased in the feces while the primary bile acids, cholic, beta-muricholic, and chenodeoxycholic acids, became predominant. Coprostanol, a microbial metabolite of cholesterol, also disappeared from the feces during the treatment. The cecum enlarged to almost twice the size of that in control rats, whereas the liver weight was not significantly changed. After treatment was stopped, the number of fecal microbes returned to the initial counts within a week, but restoration of bile acid and cholesterol metabolism required at least three weeks.

Animals↗

PubMed1983

The role of conjugation reactions in enhancing biliary secretion of bile acids.

Shortening the five-carbon carboxylic acid side chain of cholic acid by one methylene group gave rise to a bile acid (norcholate) that was not a substrate for the bile acid-conjugating enzymes. The metabolism and biliary secretion of norcholate in intact liver was examined in the isolated perfused rat liver system. When rat livers were perfused with 14-20 microM solutions of norcholate for 10 min, norcholate was found in the unconjugated form in liver, venous effluent and bile. Neither tauronorcholate nor glyconorcholate was detectable by high-pressure liquid chromatography or fast-atom-bombardment mass spectrometry. The kinetics of hepatic uptake and biliary secretion of norcholate was compared with that for cholate, taurocholate and chemically synthesized tauronorcholate. The latter three bile acids were completely cleared from the perfusate and efficiently secreted into the bile. However, norcholate was incompletely extracted from the perfusate, and this was shown to be at least partially due to its relatively lower rate of hepatic uptake. Furthermore, the rate of norcholate secretion into bile was greatly reduced relative to the secretion of cholate or chemically synthesized tauronorcholate, even though the concentration of norcholate in the liver was comparatively high. These data demonstrate that the conjugation of bile acids greatly facilitates their secretion into bile.

Animals↗

PubMed1983

Influence of dietary lipids on intestinal bile acid absorption.

The enterohepatic circulation and the inability of upper small intestine to actively absorb bile acid are physiological adaptations for maintaining adequate bile acid concentrations in the intestinal lumen for use in lipid digestion and absorption. Certain lipids inhibit bile acid absorption suggesting a possible role of lipids in this scheme. Using isolated intestinal villi preparations of hamster ileum, experiments were conducted to assess the degree of inhibition of bile acid absorption by lipids of various classes and to determine the possible mechanism of inhibition. At an initial bile acid concentration of 10.0 mM, triolein significantly reduced villus uptake of taurocholic acid by 50% and cholic acid by 38%. This inhibition was similar to the degree of inhibition produced by oleic acid (58 and 48%, respectively). Likewise, representative medium-chain and short-chain triglycerides inhibited taurocholic acid uptake by 35 and 39%, respectively. Results show that triglycerides as well as oleic acid inhibit ileal bile acid uptake. Neither oleic acid nor triolein altered bile acid uptake when micelles were absent from incubation solutions. Furthermore, lipids did not alter absorption of a nonmicelle-forming bile acid, taurodehydrocholic acid. These data imply that dietary lipids in general may inhibit intestinal bile acid absorption. Oleic acid significantly reduced the intermicellar bile acid concentration from 8.9 +/- 0.2 mM to 3.9 +/- 0.2 mM while tributyrin, tricaprylin, and triolein had no effect. Results from these studies suggest that the mechanism of inhibition appears to be an enhancement of micelle formation. We speculate that this mechanism may be an additional mechanism for maintaining adequate luminal bile acid concentrations and may be the pathophysiologic mechanism contributing to bile acid malabsorption in cystic fibrosis.

Animals↗

PubMed1997

Colon tumor promotion: is it a selective process? Effects of cholate, phytate, and food restriction in rats on proliferation and apoptosis in normal and aberrant crypts.

Promotion would suppose the selection of initiated cells. We tested the selection of aberrant crypt cells by cholic acid, a colon cancer promoter, and the effect of protectors, phytate and food restriction. After an azoxymethane injection, rats were allocated to a control diet, or to supplements of cholic acid, sodium phytate, or to a 50% food restriction. The proliferation and apoptosis of 1200 crypts were assessed, after immuno-staining for BrdU. Cholic acid increased the proliferation of aberrant crypts but not of normal crypts. Phytate and food restriction decreased the proliferation of normal crypts, but not of aberrant crypts. Apoptosis was not affected by diets. Results support the hypothesis that cholic acid can select initiated cells in the colon.

Analysis of Variance↗

PubMed1975

The removal of retained gallstones from the common bile duct: experience with sodium cholate infusion and the Burhenne catheter.

The use of cholic acid T tube infusion and of the Burhenne catheter has been investigated in the management of gallstones retained in the common bile duct following biliary surgery in 9 patients. Four of 7 patients treated with cholic acid infusion showed disappearance of the stones during treatment. The stones in a fifth subject were removed by a combination of cholic acid infusion (1 stone disappeared) and instrumentation with a Burhenne catheter (a second stone removed). Use of a Burhenne catheter was unsuccessful in 3 of 4 patients. Details of the technique of cholic acid infusion are given, and possible complications of the treatment are discussed. The use of cholic acid infusion for the dissolution of stones in the common bile duct is recommended.

Catheterization↗

PubMed1992

Effects of bile acids and bilirubin on bicarbonate secretion of isolated guinea pig antrum.

The effects of bile acids and bilirubin, which increase in blood in obstructive jaundice, on bicarbonate secretion were studied experimentally using isolated antral mucosa of the guinea pig. Antral mucosal preparations were mounted between Ussing chambers. Basal and bethanechol-stimulated secretion were measured by a pH stat device using 5 mM HCl. After 10(-4), 10(-3), and 5 x 10(-3) M taurocholic acid, 10(-4) and 10(-3) M cholic acid, and 1.2 x 10(-4) and 2.4 x 10(-4) M bilirubin conjugate were added to the serosal solution, basal and bethanechol-stimulated secretion were also measured. Taurocholic acid, at any dose, did not affect basal secretion, but bethanechol-stimulated secretion was inhibited dose dependently. Cholic acid and bilirubin conjugate did not affect basal secretion, but bethanechol-stimulated secretion was significantly inhibited. Although the addition of bile acid or bilirubin into the serosal solution under experimental conditions is not the same as obstructive jaundice, these studies suggest that the inhibition of bicarbonate secretion in the gastric mucosa may have an important role in the formation of acute gastric mucosal lesions in obstructive jaundice.

Animals↗

PubMed1990

Regulation and ligand-binding specificities of two sex-specific bile acid-binding proteins of rat liver cytosol.

Rat liver cytosolic proteins were photoaffinity labeled with the synthetic steroid [3H]methyltrienolone in order to identify and characterize hepatic proteins that may participate in the intracellular binding and transport of steroid hormones and other sterols. A male-specific and a female-specific sterol-binding protein (SBP) that migrated to the 4 S region of a sucrose gradient and had similar molecular weights (male-specific 34-kDa protein (SBP34), female-specific 31-kDa protein (SBP31] were thus identified. Experiments were undertaken to determine the biochemical basis for the sex-specific expression of these two proteins. In vivo hormonal manipulations established that the female-specific expression of SBP31 could, in part, be accounted for by the suppressive effects of androgen on SBP31 levels in male rats. In contrast, androgen stimulated expression of the male-specific SBP34, while estrogen and the estrogen-regulated continuous plasma growth hormone profile that is characteristic of adult female rats were suppressive toward this protein. Unlike several other androgen-dependent hepatic proteins, however, SBP34 did not require an intact pituitary for androgen-stimulated expression, nor was its expression stimulated by the intermittent pulses of plasma growth hormone that are characteristic of adult male rats. SBP34 and SBP31 were not induced but were suppressed to various extents by dexamethasone, phenobarbital, and clofibrate, drugs that are known to induce other hepatic proteins involved in steroid binding and metabolism. Competition experiments revealed that SBP31 has a relatively broad ligand specificity, with significant competition for [3H]methyltrienolone binding exhibited by bile acids (chenodeoxycholic acid and lithocholic acid) and a range of steroid hormones (progesterone, estradiol, testosterone, and 5 alpha-dihydrotestosterone) when present in the low micromolar range. No binding was detected with this protein toward cholesterol, triamcinolone acetonide, 5 alpha-androstan-3 alpha,17 beta-diol, cholic acid, and deoxycholic acid. In contrast, SBP34 exhibited greater binding specificity, with competition for [3H]methyltrienolone binding observed only with primary bile acids (cholic acid and chenodeoxycholic acid) and their metabolites (deoxycholic acid and lithocholic acid). On the basis of these binding specificities and the relatively high concentration of bile acids found in the liver, it is proposed that SBP31 and SBP34 function in the intracellular binding and/or transport of bile acids.

Affinity Labels↗

PubMed1994

Differential effects of cyclosporin A on transport of bile acids by rat hepatocytes: relationship to individual serum bile acid levels.

Cyclosporin A treatment has been reported to induce hepatotoxicity marked by a rise in total serum bile acid and total bilirubin. The mechanism of cyclosporin A-induced hepatotoxicity seems to be related to interference with hepatocellular transport of these substrates although this remains to be fully substantiated. The purpose of this study was to investigate whether the hepatocellular uptake of the different bile acids, in the presence of cyclosporin A, is consistent with the changes in their respective individual serum bile acid concentrations. High-performance liquid chromatography has been used to assay individual serum bile acids in cyclosporin A-treated rats at doses of 0.1, 1, and 10 mg/kg/day for 4 days. Control rats were treated with Cremophor (1 ml/kg/day). At the higher doses, cyclosporin A produced a significant increase in levels of cholic acid, taurocholic acid, chenodeoxycholic acid, and deoxycholic acid compared with controls. Serum glycocholate was unaffected even at the highest dose. Inhibition of initial rate of uptake and accumulation of [14C]cholic acid, [14C]chenodeoxycholic acid, and [14C]deoxycholic acid by isolated rat hepatocytes was consistent with the changes in their respective serum bile acids. Coincubation of rat hepatocytes with unlabeled cholic acid (100 microM), the major serum bile acid in cyclosporin A-treated rats, showed a further inhibitory effect on [14C]cholic acid and [14C]deoxycholic acid accumulation. The initial rate of uptake of [14C]glycocholate was also inhibited. However, accumulation of glycocholic acid did not show significant changes at the longer incubation times (2-30 min). In addition, coincubation of rat hepatocytes with unlabeled cholic acid (100 microM) plus cyclosporin A did not induce any inhibition of glycocholate accumulation. Together, these differences provide an explanation for the unchanged serum levels of glycocholate. In conclusion, the changes in individual serum bile acids in cyclosporin A-treated rats are consistent with the effect of this drug on their hepatocellular accumulation.

Animals↗

PubMed1981

Pathologic versus physiologic cholestasis: elevated serum concentration of a secondary bile acid in the presence of hepatobiliary disease.

Serum levels of the primary bile acids cholic and chenodeoxycholic acid are transiently elevated in normal neonates and infants; this represents a state of "physiologic cholestasis." In this study we determined, using specific radioimmunoassay, the concentration of a secondary bile acid, sulfated lithocholate, in serum obtained from healthy infants and from those with various hepatobiliary diseases. The serum levels of sulfated lithocholate were low in 69 neonates (less than 5 days of age: mean +/- SEM = 0.45 +/- 0.05 mumoles/L) and in 78 normal infants (less than one year of age: 0.49 +/- 0.02); there was no postprandial rise. These values were similar to those seen in 95 older children (0.56 +/- 0.03) and in maternal (0.49 +/- 0.04) and cord blood (0.44 +/- 0.03) of the neonates. In contrast, in patients with neonatal cholestasis of any nature there was a consistent marked rise in serum concentrations of sulfated lithocholate (mean = 4.46 +/- 0.39, P less than 0.001). In infants monitored during the course of parenteral nutrition, elevated values of sulfated lithocholate often occurred in the presence of normal results of other liver function tests. Serum sulfated lithocholate concentration is an accurate index of neonatal hepatobiliary disease; the sensitivity and specificity of this test remain to be further defined.

Biliary Tract Diseases↗

PubMed1976

Sulfate bile acids in germ-free and conventional mice.

Sulfated and non-sulfated bile acids were determined in the intestines and in the feces of 7-month-old germ-free and conventional male mice. 1. The bile acid pools in the gall bladder and small intestine were 21.13 mg/100g body weight in germ-free and 11.50 mg in conventional mice. The bile acid pools in the cecum and large intestine of germ-free mice were 3.03 mg/100 g body weight as compared to 1.24 mg in conventional mice. Fecal bile acid excretion was 2.93 mg and 4.12 mg/100 g body weight in 24 h in germ-free and conventional mice respectively. 2. The major bile acids from germ-free mice were cholic acid, alpha-muricholic acid and beta-muricholic acid. Small amounts of chenodeoxycholic and allocholic acid were also present. In addition to these primary bile acids the following secondary bile acids were identified in conventional mice: lithocholic, deoxycholic and omega-muricholic acid. 3. In both germ-free and conventional animals significant amounts of chenodeoxycholic and cholic acid were present as the 7-monosulfate esters. The sulfate esters of these bile acids did not exceed 2% of the total bile acids in the small intestine, but accounted for approximately 50% of the bile acids in the cecum and the large intestine. In contrast, the muricholic acids were nearly exclusively found in the non-sulfate fraction. 4. Alkaline hydrolysis without prior solvolysis of the sulfate esters resulted in loss of bile acids and production of artifacts. Hence, the bile acids of the mouse cannot be analysed by methods involving alkaline deconjugation unless a solvolysis step is included in the procedure.

Animals↗

PubMed1990

Renal sodium retention complicating alcoholic liver disease: relation to portosystemic shunting and liver function.

The aim of this study was to determine whether liver function and portosystemic shunting are related to renal sodium retention in alcoholic liver disease. Twenty-three studies were performed; 10 patients had ascites. Liver function was assessed from the plasma elimination rates of antipyrine, caffeine and stable isotopes of cholic acid, the latter administered both orally [2,2,4,4-2H] and intravenously [24-13C]. Portosystemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Portosystemic shunt fraction was similar in patients with and without ascites (61% +/- 16% vs. 64% +/- 11%) and unrelated to urinary sodium excretion in patients with ascites (r = -0.145). Patients with ascites had significantly lower elimination rates of all administered compounds as compared with patients without ascites (antipyrine = 0.012 +/- 0.007 vs. 0.031 +/- 0.016/hr, p less than 0.001; caffeine = 0.014 +/- 0.013 vs. 0.061 +/- 0.041/hr, p less than 0.002; intravenous cholic acid = 1.355 +/- 0.442 vs. 2.284 +/- 0.885/hr, p = 0.005; orally administered cholic acid = 2.178 +/- 0.841 vs. 4.056 +/- 1.837/hr, p = 0.007). However, urinary sodium excretion in patients with ascites was not related to the elimination constants of these compounds (r = 0.360, 0.319, 0.067, -0.073, respectively). Ascites complicating alcoholic liver disease is associated with impaired liver function but not the extent of portosystemic shunting.

Adult↗

PubMed1991

Equilibration of labelled and endogenous bile acids in patients with liver cirrhosis after administration of (24-14C)cholic and chenodeoxycholic acids.

On separate occasions (24-14C)cholic acid and (24-14C)chenodeoxycholic acid were administered intravenously to patients with liver cirrhosis and the isotope excretion in urine and faeces monitored. Bile acids in serum, urine and faeces were extracted and separated into unconjugated bile acids, glycine- and taurine conjugates, glucuronides and sulphates. Individual bile acid conjugates were separated by high-performance liquid chromatography (HPLC) and the unconjugated bile acids were separated by gas-liquid chromatography (GLC) and identified by gas chromatography-mass spectrometry (GC-MS). Individual bile acid conjugates were quantified and their isotope contents determined. In serum, isotope contents declined rapidly during the first day, followed by a markedly slow rate of reduction. In accordance with this, the excretion of isotope from the patients was found to be very slow and the routes of bile acid excretion were changed, which resulted in an increased ratio of urine/faeces isotope excretion. Studies of the ratio of labelled to endogenous bile acid conjugates indicated that a continuous transformation of the labelled compounds occurred during the period of study. As judged from serum bile acids, conjugation to glycine- or taurine conjugates was rapid. The specific activities of labelled sulphate esters were consistently lower than for other conjugates during the 300-min observation period. During the first day, the urinary bile acids contained a high proportion of unconjugated labelled bile acids, which gradually disappeared. Labelled primary bile acids were slowly converted into microbial products, mainly 7-alpha dehydroxylated derivatives. The observed slow transformations resulted in a much delayed equilibration of labelled and endogenous bile acid derivatives, which invalidates isotope techniques for calculation of kinetic data of bile acid turnover. However, the observed very slow turnover of labelled bile acids in cirrhosis, owing to the persistent high rate of intestinal absorption and low capacity for urinary excretion, makes it possible for the intestinal flora to markedly change the composition of the bile acids in the pool. Studies of endogenous urinary and faecal bile acid excretion revealed the changed route of bile acid excretion with a high urinary/faeces ratio and the decreased synthesis of bile acids in cirrhosis.

Bile Acids and Salts↗

PubMed1976

Effect of diet high in beef fat on the composition of fecal bile acids during intestinal carcinogenesis in the rat.

Two groups of 20 male Sprague-Dawley rats each were given sc 8 mg azoxymethane/kg body weight and fed a normal diet or one high in beef fat. Control groups were not given azoxymethane. Fat-control animals did not excrete more total bile acids than did the normal-control group but did excrete more deoxycholic acid as the result of increased cholic acid degradation. Azoxymethane itself caused an increase in fecal bile acid concentratation but tended to reduce the level of cholic acid degradation. Fatty acid content in the feces increased in the animals on the fat diet but was not affected by azoxymethane. A fat-diet-dependent increase was apparent in total fecal neutral steroids and a carcinogen-dependent increase in cholesterol degradation. Dietary fat and bile steroids altered by gut microflora were important interrelated factors in the intestinal carcinogenic process of this animal model.

Animals↗