A hydrophilic bile acid effects partial dissolution of cholesterol gallstones in the prairie dog

Gallstone formation and dissolution were studied in a prairie dog model of cholesterol (CH) cholelithiasis. Gallstones were induced in 49 prairie dogs by feeding 1.2% CH in a nutritionally adequate semisynthetic diet for 6 wk (period 1). At 6 wk, gallstones had developed in all animals examined. The diets were modified by reducing the amounts of CH to 0.4, 0.2, 0.1 and 0.0% (diets 1–4); hyodeoxycholic acid (HDA; 30 mg/kg/day) was added to these diets (diets 5–8). All animals were fed the modified experimental diets for an additional 8 wk (period 2). At week 14, spontaneous gallstone dissolution had not occurred, even in the groups given no added dietary CH during period 2 (group 4). Addition of HDA to the diet tended to reduce the incidence of biliary CH crystals and the size and number of CH gallstones. Biliary CH remained elevated and the lithogenic indices in all groups were found to be greater than 1.0 at the end of the experiment. Liver and plasma CH levels tended to be lower in the groups fed HDA. In these groups, HDA and 6βHDA became the major biliary bile acids. This study demonstrates that HDA achieved partial dissolution of gallstones in bile supersaturated with CH.     

Hydroxylation of secondary bile acids in the perfused prairie dog liver

Taurolithocholic acid and deoxycholic acid were perfused into isolated prairie dog livers. Taurolithocholic acid was 7α-hydroxylated to form taurochenodeoxycholic acid, whereas deoxycholic acid was conjugated and 7α-hydroxylated to form taurocholic acid. The low concentrations of secondary bile acids observed in prairie dog bile are due, at least in part, to active bile acid 7α-hydroxylase(s) in the liver of these animals.     

Effect of previous nutritional status on the formation of cholesterol gallstones in the prairie dog

In the prairie dog model of cholesterol cholelithiasis, a high incidence of gallstones is achieved by feeding a semipurified lithogenic diet containing 0.4% cholesterol for 2 mo. On occasion, we noted a decrease in the percentage of animals with gallstones from 90–100% to 50–55%. To explain this phenomenon, we studied the effect of dietary history on gallstone formation. After weaning, animals were fed either rodent chow or alfalfa plus corn (mo 0–3) followed by a cross-over experiment at mo 4–6. Gallstone formation then was studied by feeding the lithogenic diet from mo 7 to 8. At sacrifice, the incidences of gallstones, biliary lipids and tissue cholesterol levels were correlated with dietary history. The incidence of gallstones was 100% only in animals fed the alfalfa-corn diet from weaning to 3 mo. In addition, the feeding of the alfalfa-corn diet at mo 4–6 increased gallstone incidence from 65% to 86%. The lithogenic index of all groups was highest when the animals received only alfalfa-corn prior to the lithogenic stimulus. The activity of hepatic HMG-CoA reductase was elevated in animals fed alfalfa-corn from weaning to 8 mo, suggesting that this diet stimulates hepatic cholesterol synthesis, leading to increased biliary cholesterol secretion. It is concluded that previous nutritional conditioning affects the incidence of gallstones. The prairie dog is a useful model of cholesterol cholelithiasis, but the dietary history of the animals plays an important role in lithogenesis.     

The effect of alfalfa-corn diets on cholesterol metabolism and gallstones in prairie dogs

Cholesterol gallstones were present in prairie dogs fed alfalfa plus corn with and without exogenous cholesterol (0.4%). The diets fed to the animals for eight weeks contained alfalfa plus corn in fixed proportions of 50∶50, 85∶15 and 15∶85 (w/w). At sacrifice, all animals were healthy but had not gained weight; no deaths occurred during the experiment. Cholesterol gallstones were present in all groups. In the absence of exogenous cholesterol, the highest stone incidence was found in the animals which received the lowest fiber (highest corn) diets (alfalfa plus corn, 50∶50, 67%; alfalfa plus corn, 15∶85, 83%). Cholesterol gallstone incidence was 100% when exogenous cholesterol was added to the alfalfa plus corn diets (50∶50 and 15∶85). No pigment gallstones were detected in any animal. Liver and plasma cholesterol concentrations were highest in the animals receiving alfalfa plus corn (15∶85) plus 0.4% cholesterol (4.29 mg/g, and 356 mg/dl, respectively). These values were lowest in animals receiving 85% alfalfa plus 15% corn without cholesterol (2.19 mg/g and 88 mg/dl, respectively). Lithogenic indices were below 1.00 in all groups. Biliary bile acids were mainly amidates of cholic acid and chenodeoxycholic acid, with the former predominating. Thus, gallstones can be formed in prairie dogs in the absence of exogenous cholesterol; gallstone incidence is reduced by dietary fiber.     

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-chenodeoxy-cholic acid, 7β-methyl-24-nor-5β-cholestane-3α,7α,25-triol, cholic acid, 7-methyl-cholic acid, or 7β-methyl-24-nor-5β-cholestane-3α,7α,12α,25-tetrol. Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and β-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.     

Effect of dietary bile acids,cholesterol, and β-sitosterol upon formation of coprostanol and 7-dehydroxylation of bile acids by rat

During studies of sterol metabolism in the rat, the fecal neutral sterol fraction was analyzed by a combination of thin layer chromatography and gas liquid chromatography. On a stock diet of rat chow supplemented with 5% corn oil, the rats excreted 14.5 mg/day of total neutral sterols. Coprostanol comprised 35% (5 mg/day) of this fraction. When the diet was supplemented with 0.5% sodium taurochenodeoxycholate, the amount of coprostanol in the feces remained the same as in the controls (3.2 mg/day, 32%). The addition of 0.5% sodium taurocholate to the diet resulted in a fivefold reduction of coprostanol formation (0.6 mg/day, 8%). When 1.2% cholesterol was added to the stock diet, the amount of coprostanol present in the feces decreased to an average of 11% compared to controls, but the absolute amount formed was greater (35 mg/day). On a diet enriched with 0.8% β-sitosterol, the rats, on the average, converted 23% of the cholesterol to coprostanol. Feeding diets enriched with sodium taurochenodeoxycholate and sodium taurocholate reduced the 7-dehydroxylation of primary bile acids in the feces by 28% and 42%, respectively. The conversion of primary bile acids to secondary bile acids in the feces of control, cholesterol, and β-sitosterol fed rats was the same (64%).     

The effects of polyoxyethylated cholesterol on fecal bile acids and nitrogen and on cholesterol balance in rats

Polyoxyethalated cholesterol (POEC) is a water soluble derivative of cholesterol which decreases cholesterol absorption in rats without affecting body weight, fatty acid excretion, or intestinal histology. In the present study rat feces were analyzed for cholic, deoxycholic, chenodeoxycholic, muricholic and lithocholic acid following 3 months of feeding a standard or a 2% enriched cholesterol diet with or without 1.5% POEC. In rats maintained on the cholesterol free diet, POEC increased total bile acids (mg/day) by 50% from 14±3 to 21±3 (mean ±SEM) but only the increase in chenodeoxycholic acid was significant (P<0.05). The corresponding POEC effect in the 2% cholesterol diet was 31% (70±8 to 93±3, P<0.01). Fecal nitrogen and serum cholesterol did not vary among groups. Comparing these data with neutral steroid excretion previously determined showed that POEC in the cholesterolfree diet increased the negative cholesterol balance more than three-fold (34±7vs 118±13 P<0.01). In rats fed 2% cholesterol, POEC caused a negative cholesterol balance of 222±8 compared to the control of 27±52 (P<0.01). The data indicate that POEC exerts complex effects in the intestinal tract which increase both bile acid and cholesterol excretion.     

Effects of cholesterol feeding to maternal rats on metabolism of cholesterol and bile acids in the dams and their offspring

The influence of feeding cholesterol to rats during pregnancy and postpartum (from the 11th day of gestation to the third day after delivery) on the serum and hepatic cholesterol levels and on the bile acid composition in the pool and in the liver in relationship to the dams and their pups was examined. The hepatic content of cholesterol in both dam and offspring increased during cholesterol feeding without any changes in serum cholesterol level. In the dams, mainly the esterified cholesterol was increased; in the pups, mainly the free cholesterol was increased. Cholesterol feeding led to a pronounced increase in the pool of β-muricholic acid and a relative decrease in the lithocholic acid concentration in pregnant rats. In fetal rats, the chenodeoxycholic acid pool was increased by cholesterol intake. The lithocholic acid pool was larger in the postpartum rats fed cholesterol than in the controls, while the concentration of α- and β-muricholic acids was decreased. The neonates of cholesterol-fed dams had a larger pool of chenodeoxycholic acid but a smaller pool of β-muricholic acid. These results suggest that the metabolism of cholesterol and of bile acids in dams and their offspring respond differently to cholesterol intake.     

The effect of neurotensin on the concentration of cholesterol and bile acids in the guinea pig

In guinea pigs, total plasma cholesterol concentrations increased above the control values after single intravenous injections and after 3 days of continuous subcutaneous administration of neurotensin (NT). A high dose of NT (125 pmol/100 g body weight) induced tachycardia and severe respiratory distress; the lowest dose (1.25 pmol/100 g body weight) had the greatest hypercholesterolemic effect 15 min after the injections. The bulk of the total plasma cholesterol was in low density lipoprotein fractions. Cholesterol increased in the same fractions after intravenous administrations of NT. NT induced a decrease in the cholesterol content in the ileum but did not affect significantly the cholesterol content in the liver, kidneys or adrenals. In 48-hr fasted controls, plasma cholesterol concentration and cholesterol content in the liver, kidneys, adrenals and terminal ileum increased; after intravenous injections of NT, plasma cholesterol concentration further increased but cholesterol content of the liver, kidneys and ileum decreased. In fed animals, the concentration of the biliary taurochenodeoxycholic acid increased above the control values 5 and 35 min after the intravenous injections of NT. In fasted controls, the total concentration of bile acids was higher than in fed controls, but only the concentration of taurochenodeoxycholic acid further increased after the injections of NT. Proportionately more taurochenodeoxycholic acid than cholesterol was present in bile after the intravenous injections of NT. These data are consistent with the hypothesis that NT has a regulatory role in intestinal cholesterol transport.     

Regulation of 3-hydroxy-3-methylglutaryl CoA reductase by analogs of cholesterol and bile acids in cultured intestinal mucosa

Sodium fusidate and its glycine conjugate, which have the same detergent properties as bile acids, significantly (p<0.05) stimulate HMG-CoA reductase of cultured intestine below the critical micellar concentration (CMC) without affecting brush border enzymes. Above CMC, both amphiphiles are cytotoxic. At concentrations between 1 and 5 mM, sodium fusidate decreased cholesterol contents of cultured mucosa (p<0.05), the increase in synthesis only partially compensating for the sterol loss. Oxygenated sterols, 7-keto- and 25-hydroxycholesterol, also depleted mucosal cholesterol at 0.5 mM, exerting their effect differently by inhibiting HMG-CoA reductase (p<0.01). In contrast to their marked effect on total mucosal cholesterol contents, brush border cholesterol was unaffected by both cholesterol and bile acid analogs.     

Effects of feeding chenodeoxycholic acid on metabolism of cholesterol and bile acids in germ-free rats

The aim of this investigation was to study the influence of chenodeoxycholic acid administration on cholesterol and bile acid synthesis in germ-free rats. Seven rats were fed a basal diet and 2 groups of 4 rats received the same diet supplemented with 0.4 and 1% chenodeoxycholic acid, respectively. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis of cholesterol and bile acids. When the sampling period was finished, the rats were killed and the liver microsomal fractions isolated. The activities of HMG CoA reductase and cholesterol 7α-hydroxylase were determined, the 7α-hydroxylase by a mass fragmentographic method. The 2 dominating bile acids in the untreated rats were cholic acid and β-muricholic acid. During treatment with chenodeoxycholic acid, 60–70% of this bile acid was converted into α- and β-muricholic acid, indicating a high activity of the 6β-hydroxylase. The excretion of cholic acid was almost completely inhibited and the 7α-hydroxylase activity was decreased ca 75% in the rats fed 1% chenodeoxycholic acid. The activity of the hepatic HMG CoA reductase was unchanged. The fecal excretion of cholesterol increased 2–3 times. An accumulation of cholesterol was seen in the rats treated with 1% chenodeoxycholic acid, which was probably a result of the decreased catabolism of cholesterol to bile acids.     

Hydrophilic bile acids: Prevention and dissolution experiments in two animal models of cholesterol cholelithiasis

The effects of β-muricholic acid and hyocholic acid on cholesterol cholelithiasis were examined in two animal models. The following experiments were carried out: A) In a gallstone prevention study, prairie dogs were fed the lithogenic diet with or without 0.1% β-muricholic or 0.1% hyocholic acid for eight weeks. B) In a second prevention study, hamsters were fed the lithogenic diet with or without 0.1% β-muricholic acid or 0.1% hyocholic acid for six weeks. C) In a gallstone dissolution study, hamsters were fed the lithogenic diet for six weeks to induce stones; stone dissolution was examined during administration of a cholesterol-free purified diet with or without 0.1% β-muricholic acid or 0.1% hyocholic acid. In the prevention study in prairie dogs (A), both bile acids failed to prevent stone formation, the cholesterol saturation index of bile was 0.89 in the lithogenic controls, remained unchanged with hyocholic acid and increased to 1.52 in the β-muricholic acid group. In the prevention study in hamsters (B), β-muricholic acid completely inhibited the cholesterol cholelithiasis (0% stone incidence); the cholesterol saturation index of bile was 1.78 (compared to lithogenic controls, 1.37). Hyocholic acid reduced stone incidence to 16% with a cholesterol saturation index of 0.98. In the dissolution study in hamsters (C), preexisting cholesterol gallstones were not dissolved by either hydrophilic bile acid after feeding these bile acids for an additional six weeks; at the end of the experiment, the cholesterol saturation indices were below unity. These studies suggest that, in the hamster animal model, hydrophilic bile acids may be useful for the prevention of gallstones but not dissolution of preestablished cholesterol gallstones.     

Effects of ethylp-chlorophenoxyisobutyrate on biliary secretion of bile acids,cholesterol and phosphatidyl choline

The effect of chronic administration of ethylp-chlorophenoxyisobutyrate (CPIB) on the secretion of bile lipids was studied in four dogs with surgically implanted Thomas cannulae for periods of 2–7 months. The concentration of cholesterol, triglycerides andp-chlorophenoxyisobutyric acid in serum and of bile acids, cholesterol and phospholipids (phosphatidyl cholines) in bile were measured. Chronic administration of CPIB resulted in a marked increase in the concentration of cholesterol, bile acids and phosphatidyl cholines in the bile of all dogs, and a decrease in serum cholesterol and triglyceride concentration in serum in three of the four dogs. Serum concentrations ofp-chlorophenoxyisobutyric acid were monitored to insure the presence of the drug in the dogs; however, no correlation between serum levels ofp-chlorophenoxyisobutyric acid and the concentration of biliary lipids was noted. The bile acids andp-chlorophenoxyisobutyric acid were determined by gas chromatographic procedures and the structures were confirmed by gas chromatography-mass spectrometry. One of eight papers presented at the symposium “Recent Advances in Drugs Affecting Lipid Metabolism,” AOCS Meeting, Houston, May 1971.     

Dissolution kinetics of chromite overburden by using mineral acids

Two different mineral acids were used to determine the kinetics of dissolution of Ni and Fe from chromite overburden. Various leaching parameters were studied such as acid concentration, pulp density, temperature and particle size. Both Fe and Ni dissolution followed 1st order irreversible kinetics. The activation energy was also measured. Unified rate equations were established for Ni and Fe dissolution for two different mineral acids, HCl and H₂SO₄. The dissolution reaction was observed to follow diffusion control-dense-constant size spherical particles.     

Dissolution characteristics of hectorite in inorganic acids

The effect of acid type (HCl, HNO₃ and H₂SO₄) and concentration on the dissolution rate of hectorite were monitored through chemical analyses and XRD. The rate of dissolution increased with increasing acid concentration during the first 2–4 h of contact. After that time, the correlation between acid concentration and the amounts of dissolved elements strongly decreased and often higher concentrations were found in 0.25 M solutions than in 1 M solutions. The monitoring of the amount of Si is somewhat more complex since it is the result of two processes: release from the mineral and reprecipitation as an amorphous end product. In the case of HCl, the behavior of Li, Mg and Fe differed from their behavior in the other acids, but further research is necessary to characterize the reactions that may occur. From the half times of dissolution, the dissolution curves and the XRD data, it could be concluded that the dissolution rate of hectorite decreased in the order H₂SO₄>HNO₃≥HCl at the same molar concentration, which is the reverse of what was found by other investigators. After 8 h, for example, the 1 M H₂SO₄ treatment dissolved more than 70% of all Li present in the hectorite, whereas equal molar HNO₃ and HCl dissolved 58% and 53%, respectively. Oriented XRD patterns only showed a background scatter after 6 h of contact with 0.25 M H₂SO₄ and after 4 h using a concentration of 1 M H₂SO₄. Treatments with 0.25 M HNO₃ and 0.25 M HCl still gave reflections after 6 h and even after 8 h, the d(001) XRD peak could still be observed. In 1 M HNO₃ and 1 M HCl, no more reflections could be seen after 4–6 h. At that time, XRD powder patterns showed that the crystal structure was still partly preserved in the a- and b-direction of the mineral. It must be stressed that absence or a decrease in intensity of the d(001) peaks may not be fully assigned to the breakdown of the mineral structure since the Si, extracted from the lattice reprecipitates as amorphous silica, which may disrupt the layer stacking and decrease the coherence of the reflections. For the comparison of the three acids on a normal basis, the quarter times of dissolution were found to be a more appropriate tool than the half times of dissolution. The results showed that the differences among the three acids were rather small and that the concentration of the acids was the main parameter affecting the dissolution rate of the hectorite, in particular, in the beginning of the treatment.     

Effects of bile acid oxazolines on gallstone formation in prairie dogs

The effects of 2 bile acid analogs, chenodeoxy-oxazoline [2-(3α,7α-dihydroxy-24-nor-5β-cholanyl)-4,4-dimethyl-2-oxazoline] and ursodeoxy-oxazoline [2-(3α, 7β-dihydroxy-24-nor-5β-cholanyl)-4,4-dimethyl-2-oxazoline] were examined in the prairie dog model of cholesterol cholelithiasis. Gallstones and biliary cholesterol crystals were induced in 5 out of 6 male prairie dogs fed a semisynthetic diet containing 0.4% cholesterol for 8 weeks. Six animals maintained on a low cholesterol control diet (0.08% cholesterol) exhibited neither gallstones nor biliary cholesterol crystals. The addition of 0.06% chenodeoxy-oxazoline to the lithogenic diet did not prevent induced cholelithiasis or the appearance of cholesterol crystals in bile. In contrast, 0.06% dietary ursodeoxy-oxazoline prevented gallstones in 5 out of 6 prairie dogs (but cholesterol crystals were present in the bile of 4 of these animals). Histologically, most of the livers from the prairie dogs fed the cholesterol-supplemented semisynthetic diet showed bile duct proliferation, inflammatory infiltration and fibrosis along the portal tracts. These pathologic changes were generally not ameliorated by adding chenodeoxy-oxazoline or chenodeoxy-oxazoline plus chenodeoxycholic acid to the diet. Portal tract pathology was markedly reduced in most animals by adding ursodeoxy-oxazoline to the cholesterol-supplemented diet. The pathologic changes overall could best be correlated with the presence of gallstones, but not with the incidence of biliary cholesterol crystals.     

Dietary induction of cholesterol gallstones in hamsters from three different sources

Cholesterol gallstones were produced in young male, golden Syrian hamsters, obtained from three different suppliers, by administering a nutritionally adequate, semipurified diet for periods of either 5 or 10 weeks. The major components of the lithogenic diet were casein, cornstarch, butterfat, corn oil and 0.3% cholesterol. The hamsters were obtained from Sesco, Harlan Sprague-Dawley (Engle hamster) and Charles River (Lakeview hamster). There were profound differences among the three groups with respect to gallstone formation and cholesterol metabolism: The highest incidence of gallstones occurred in Sesco hamsters, 44.4% and 63.6% after 5 and 10 weeks on the lithogenic diet, respectively. In the Engle hamster, after a 5-week feeding, cholesterol crystals and gallstones were absent. When the feeding period was extended to 10 weeks, cholesterol gallstones were present in 45.5% of the animals. In the Lakeview hamsters, neither gallstones nor cholesterol crystals were found in the gallbladder after a 5-week period. After 10 weeks, cholesterol gallstones were found in only a single hamster. In all groups, the lithogenic diet produced large increases of liver, serum and biliary cholesterol concentrations and increased liver weights. When the animals were fed for 5 weeks, only the bile of Sesco hamsters became supersaturated. Supersaturated bile was induced in all groups after a 10-week feeding of the lithogenic diet with cholesterol saturation ranging from 1.47 to 1.97. These data indicate that it is possible to induce cholesterol gallstones in hamsters by means of a nutritionally adequate, semipurified diet of moderate cholesterol content. The source of the animals appears to be an important variable, because there were significant differences among the hamsters of differing origins, in cholesterol metabolism and rates of gallstone formation.     

Composition of bile acids in ruminants

The bile acids found in sheep bile, beef bile, beef feces, sheep fetus bile, and beef fetus bile have been analyzed by using conventional techniques. Animals maintained on natural and purified diets were used. The bile acids are a complex mixture of isomeric hydroxy- and keto-5β-cholanoic acids which were substituted at one or several of the carbon atoms 3, 7, and 12. Cholic acid is the predominant bile acid found in these species. Deoxycholic acid was the major product formed from cholic acid when the animals were on a natural diet but the concentration of 3α, 12α-dihydroxy-7-keto-5β-cholanoic acid was elevated in the animals that were maintained on a high concentrated purified diet (without roughage). The fetus bile was found to contain nearly all of the bile acids found in the bile of the mature animal but in different concentrations.     

Distribution of bile acids in rats

Distribution and biliary and fecal excretion of bile acids were examined in Wistar strain male rats of about 300 g body weight. The pool size of the rats on ordinary diet was 40 mg/rat, biliary secretion was 14 mg/hr, and fecal excretion was 10 mg/day. Bile acids were mainly located in the small and large intestinal contents, 87% and 10%, respectively; but a portion was found in the intestinal wall and the liver. Rats fed 2% cholesterol-supplemented diet for a week showed similar values for pool size and biliary secretion with the rats on ordinary diet, but higher values for fecal excretion and distribution ratio in the large intestinal contents. Cholic acid was a major component in the bile, small intestinal wall, small intestinal content and liver, while the bile acid composition ratios were roughly similar to each other, although a relatively large amount of α-muricholic acid was found in the intentinal wall and liver. Both the wall and content compositions of the large intestine were similar to that of the feces, in which lithocholic, deoxycholic, α- and β-muricholic acids were the main components, although the ratios of α- and β-muricholic acids in the large intestinal wall were larger than those in the intestinal contents or feces. The high concentrations of these bile acids may indicate a difference of transport velocity across the cell membrane, but the mechanism is not known.     

Evidence for distinct precursor pools for biliary cholesterol and primary bile acids in cebus and cynomolgus monkeys

The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones. To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein free¹⁴C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus). After total bile acid pool washout, monkeys were infused with human LDL or HDL labeled with free¹⁴C-cholesterol, and the specific activities (SA) of biliary cholesterol and primary bile acid conjugates were determined. In both species, regardless of the lipoprotein infused, the SA of biliary cholesterol and CA were greater than those for total bile acids and CDCA, respectively. In cynomolgus, the SA of glycine conjugates was higher for CA than CDCA, while the SA of taurine conjugates was greater for CDCA than CA. Under these conditions, (i) infused lipoprotein free cholesterol (as either LDL or HDL) contributed more to biliary cholesterol than to bile acids and more to CA than to CDCA; (ii) glycine conjugated preferentially with CA rather than CDCA, while taurine was the preferred conjugate for CDCA. Further, whereas the two primary bile acids had similar rates of synthesis and turnover in cynomolgus, basal bile acid synthesis was much greater in cebus and the CDCA turnover appeared disproportionately large.