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• W2123145802 abstract "This study investigated whether β-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or β-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% β-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of β-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of β-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%).We conclude that β-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice. This study investigated whether β-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or β-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% β-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of β-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of β-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that β-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice. Cholesterol gallstones are a major public health problem in all developed countries. In the United States, approximately 10–15% of the adult population suffers from cholesterol gallstones (1Diehl A.K. Epidemiology and natural history of gallstone disease.Gastroenterol. Clin. North Am. 1991; 20: 1-19Abstract Full Text PDF Google Scholar, 2Everhart J.E. Khare M. Hill M. Maurer K.R. Prevalence and ethnic differences in gallbladder disease in the United States.Gastroenterology. 1999; 117: 632-639Google Scholar), which constitutes one of the most common and most costly digestive diseases (3NIH Consensus conferenceGallstones and laparoscopic cholecystectomy.JAMA. 1993; 269: 1018-1024Google Scholar). Long-term administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to promote the dissolution of cholesterol gallstones (4Tokyo Cooperative Gallstone Study GroupEfficacy and indications of ursodeoxycholic acid treatment for dissolving gallstones. A multicenter double-blind trial.Gastroenterology. 1980; 78: 542-548Abstract Full Text PDF Google Scholar) and to prevent the recurrence of gallstones after extracorporeal shock wave lithotripsy (5Sackmann M. Niller H. Klueppelberg U. von Ritter C. Pauletzki J. Holl J. Berr F. Neubrand M. Sauerbruch T. Paumgartner G. Gallstone recurrence after shock-wave therapy.Gastroenterology. 1994; 106: 225-230Abstract Full Text PDF Google Scholar). Therapeutic mechanisms of UDCA include decreasing biliary secretion and intestinal absorption of cholesterol (6Bachrach W.H. Hofmann A.F. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Parts I and II.Dig. Dis. Sci. 1982; 27 (833–856): 737-761Google Scholar, 7Ponz de Leon M. Carulli N. Loria P. Iori R. Zironi F. Cholesterol absorption during bile acid feeding. Effect of ursodeoxycholic acid (UDCA) administration.Gastroenterology. 1980; 78: 214-219Google Scholar), both of which could contribute to a decrease in bile cholesterol saturation. However, UDCA constitutes only ∼50% of the biliary bile acid pool in patients with cholesterol gallstones (8Carulli N. Ponz de Leon M. Zironi F. Pinetti A. Smerieri A. Iori R. Loria P. Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short term feeding of chenodeoxycholic and ursodeoxycholic acid.J. Lipid Res. 1980; 21: 35-43Google Scholar, 9Hofmann A.F. Medical treatment of cholesterol gallstones by bile desaturating agents.Hepatology. 1984; 4: 199S-208SGoogle Scholar). The human intestinal bacteria can transform UDCA to lithocholic acid (10Bazzoli F. Fromm H. Sarva R.P. Sembrat R.F. Ceryak S. Comparative formation of lithocholic acid from chenodeoxy-cholic and ursodeoxycholic acids in the colon.Gastroenterology. 1982; 83: 753-760Google Scholar, 11Fedorowski T. Salen G. Tint G.S. Mosbach E. Transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal bacteria.Gastroenterology. 1979; 77: 1068-1073Google Scholar) that is shown to be a hepatotoxic bile acid to laboratory animals (12Miyai K. Javitt N.B. Gochman N. Jones H.M. Baker D. Hepatotoxicity of bile acids in rabbits: ursodeoxycholic acid is less toxic than chenodeoxycholic acid.Lab. Invest. 1982; 46: 428-437Google Scholar). β-muricholic acid (3α,6β,7β-trihydroxy-5β-cholan-24-oic acid) is a natural trihydroxy hydrophilic bile acid, which is a major bile acid biosynthesized by rat (13Kellogg T.F. Wostmann B.S. Fecal neutral steroids and bile acids from germfree rats.J. Lipid Res. 1969; 10: 495-503Google Scholar) and mouse (14Wang D.Q-H. Lammert F. Cohen D.E. Paigen B. Carey M.C. Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis.Am. J. Physiol. 1999; 276: G751-G760Google Scholar) liver and found in their bile. Because of the presence of a hydroxy group in the 6β position of the steroid ring, β-muricholic acid (15Montet J.C. Parquet M. Sacquet E. Montet A.M. Infante R. Amic J. β-Muricholic acid; potentiometric and cholesterol-dissolving properties.Biochim. Biophys. Acta. 1987; 918: 1-10Google Scholar) is more hydrophilic than UDCA. In vitro studies (15Montet J.C. Parquet M. Sacquet E. Montet A.M. Infante R. Amic J. β-Muricholic acid; potentiometric and cholesterol-dissolving properties.Biochim. Biophys. Acta. 1987; 918: 1-10Google Scholar) have demonstrated that β-muricholic acid can dissolve solid cholesterol monohydrate crystals via formation of a liquid crystalline mesophase, suggesting that it may be used to dissolve cholesterol gallstones. However, Cohen et al. (16Cohen B.I. Mikami T. Ayyad N. Ohshima A. Infante R. Mosbach E.H. Hydrophilic bile acids: prevention and dissolution experiments in two animal models of cholesterol cholelithiasis.Lipids. 1995; 30: 855-861Google Scholar) found that feeding low (0.1%) dose of β-muricholic acid for 6 weeks does not dissolve preexisting gallstones in prairie dogs or hamsters. Moreover, feeding 0.1% β-muricholic acid inhibits gallstone formation in hamsters, but fails to prevent gallstone formation in prairie dogs (16Cohen B.I. Mikami T. Ayyad N. Ohshima A. Infante R. Mosbach E.H. Hydrophilic bile acids: prevention and dissolution experiments in two animal models of cholesterol cholelithiasis.Lipids. 1995; 30: 855-861Google Scholar). Therefore, in this study we compared physical-chemical properties of β-muricholic acid with UDCA and investigated i) whether β-muricholic acid acts as a potent biliary cholesterol-desaturating agent to prevent cholesterol gallstone formation in gallstone-susceptible C57L mice carrying Lith genes (17Wang D.Q-H. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile.J. Lipid Res. 1997; 38: 1395-1411Google Scholar); ii) whether it facilitates the dissolution of cholesterol gallstones; and iii) how it regulates hepatic and biliary cholesterol and bile salt metabolism. Our results showed that β-muricholic acid is more effective than UDCA in preventing cholesterol gallstones through inhibiting intestinal cholesterol absorption, decreasing biliary cholesterol secretion, and retarding phase separation from vesicular cholesterol to crystalline cholesterol monohydrate in bile of C57L mice. Also, it is more successful than UDCA in promoting the dissolution of cholesterol gallstones through a greater capacity to form a liquid crystalline phase. Therefore, we conclude that β-muricholic acid could be a potential cholelitholytic agent for preventing or treating diet-induced or experimental cholesterol gallstones in mice. Cholic acid, UDCA, taurocholate, tauroursodeoxycholate, and cholesterol were purchased from Sigma Chemical (St. Louis, MO), and grade I egg yolk lecithin was from Lipid Products (South Nutfield, Surrey, UK). Sodium tauro-β-muricholate and β-muricholic acid were obtained from Tokyo Tanabe (Tokyo, Japan), and its purity was >98% as determined by high performance liquid chromatographic (HPLC) and thin layer chromatographic analyses. Intralipid (20%, w/v) was purchased from Pharmacia (Clayton, NC), and medium-chain triglyceride was from Mead Johnson (Evansville, IN). Radioisotope [1,2-3H]cholesterol, [4-14C]cholesterol, DL-[5-3H]mevalonolactone, and DL-[3-14C]HMG-CoA were purchased from NEN Life Science Products, (Boston, MA), and [5,6-3H]sitostanol was from American Radiolabeled Chemicals (St. Louis, MO). For HPLC analyses of bile salt species and cholesterol, all reagents were HPLC grade and obtained from Fisher Scientific (Fair Lawn, NJ). All other chemicals and solvents were American Chemical Society (ACS) or reagent grade quality (Fisher Scientific, Medford, MA). Male C57L/J mice, 6–8 weeks old, were purchased from The Jackson Laboratory, Bar Harbor, ME. C57L strain is homozygous for susceptible Lith alleles (17Wang D.Q-H. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile.J. Lipid Res. 1997; 38: 1395-1411Google Scholar). All animals were maintained in a temperature-controlled room (22 ± 1°C) with 12-h day cycles (6 AM-6 PM), and were allowed to adapt to the environment for 2-weeks prior to the experiments, and were provided free access to water and normal mouse chow containing trace cholesterol (<0.02%) (The Mouse Diet 1401, St. Louis, MO). To make semisynthetic diets, cholesterol and bile acids were added to powdered chow in ethanol, blended thoroughly with a mechanical mixer, and dried on trays at 50°C for 48 h. For gallstone prevention study, mice were divided into three groups (n = 20 each) fed a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or 0.5% β-muricholic acid for 8 weeks. In our initial study, we have observed that at week 8 of 1% cholesterol and 0.5% cholic acid feeding, 80% of male C57L mice formed gallstones, and 2% cholesterol plus 0.5% cholic acid induces 100% of C57L mice forming cholesterol gallstones. For gallstone dissolution study, additional groups (n = 20 each) of mice that have formed cholesterol gallstones due to the 8-week feeding of 2% cholesterol and 0.5% cholic acid, were fed chow (control) with or without 0.5% UDCA or 0.5% β-muricholic acid for 8 weeks. All experiments were executed according to accepted criteria for the care and experimental use of laboratory animals and euthanasia was consistent with recommendations of the American Veterinary Medical Association. All protocols were approved by the Institutional Animal Care and Use Committees of Harvard University and Hiroshima University. At week 8 of the semisynthetic diets (see above) feeding, non-fasted animals were weighed and anesthetized with an ip injection of 35 mg/kg pentobarbital. After cholecystectomy, gallbladder volume was measured by weighing the whole gallbladder and equating gallbladder weight (including stones) with gallbladder volume (17Wang D.Q-H. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile.J. Lipid Res. 1997; 38: 1395-1411Google Scholar). Gallbladders were then opened, and 5 μl of fresh gallbladder bile were examined for mucin gel, solid and liquid crystals, and gallstones, which were defined according to previously established criteria (14Wang D.Q-H. Lammert F. Cohen D.E. Paigen B. Carey M.C. Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis.Am. J. Physiol. 1999; 276: G751-G760Google Scholar, 17Wang D.Q-H. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile.J. Lipid Res. 1997; 38: 1395-1411Google Scholar). After pooled gallbladder biles were centrifuged at 100,000 g for 30 min at 37°C and filtered through a preheated (37°C) Swinnex-GS filter (0.22 μm) assembly (Millipore Products Division, Bedford, MA), samples were frozen and stored at −20°C for further lipid analyses (see below). Additional groups of mice (n = 5 each) fed the semisynthetic diets were used for biliary lipid secretion study (18Wang D.Q-H. Lammert F. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice. Pathophysiology of biliary lipid secretion.J. Lipid Res. 1999; 40: 2066-2079Google Scholar). In brief, after cholecystectomy, the common bile duct was cannulated via a PE-10 polyethylene catheter. Hepatic bile was collected by gravity. The first hour collection of hepatic biles was used to study biliary lipid outputs. To determine the circulating bile salt pool sizes, 8-h biliary “washout” studies were performed according to previously described methods (18Wang D.Q-H. Lammert F. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice. Pathophysiology of biliary lipid secretion.J. Lipid Res. 1999; 40: 2066-2079Google Scholar). After fresh hepatic biles were examined by polarizing light microscopy and their volumes were determined by weighing, samples were frozen and stored at −20°C for further lipid analyses. During surgery and hepatic bile collection, mouse body temperature was maintained at 37 ± 0.5°C with a heating lamp and monitored with a thermometer. Cholesterol absorption was determined by a plasma dual isotope ratio method (14Wang D.Q-H. Lammert F. Cohen D.E. Paigen B. Carey M.C. Cholic acid aids absorption, biliary secretion, and phase transitions of cholesterol in murine cholelithogenesis.Am. J. Physiol. 1999; 276: G751-G760Google Scholar, 19Wang D.Q-H. Paigen B. Carey M.C. Genetic factors at the enterocyte level account for variations in intestinal cholesterol absorption efficiency among inbred strains of mice.J. Lipid Res. 2001; 42: 1820-1830Google Scholar) in mice (n = 10 per group) fed chow, or chow containing 0.5% (by weight) of UDCA, cholic, or β-muricholic acids for 7 days. In brief, non-fasted mice were anesthetized by ip injection of 35 mg/kg pentobarbital. One hundred microliters of Intralipid containing 2.5 μCi of [3H]cholesterol was injected (iv) into the jugular vein. Following this procedure, the animal was given by gavage an intragastric (ig) dose of 1 μCi of [14C]cholesterol mixed with 150 μl of medium-chain triglyceride. After dosing, mice were returned to individual cages with wire mesh bottoms, where they were free to eat chow or the appropriate semisynthetic diets for an additional 3 days. Mice were then anesthetized as described above, and were bled from the heart into heparinized microtubes. Ten microliters of EcoLite (ICN Biomedicals, Costa Mesa, CA) were mixed with 100-μl portions of plasma and the original dosing mixture, respectively. The vials were counted in a liquid scintillation spectrometer (Beckman Instruments, San Ramon, CA). The ratio of the two radiolabels in plasma was used for calculating the percent cholesterol absorption: Liver samples were harvested from non-fasted mice (n = 5 per group) at week 8 of feeding of chow or the semisynthetic diets. To minimize diurnal variations of hepatic enzyme activities, all procedures (20Lammert F. Wang D.Q-H. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: integrated activities of hepatic lipid regulatory enzymes.J. Lipid Res. 1999; 40: 2080-2090Google Scholar) were performed between 8 AM and 9 AM. Microsomal activities of HMG-CoA reductase were determined by measuring the conversion rate of [14C]HMG-CoA to [14C]mevalonic acid using a radiochemical assay (21Doerner K.C. Gurley E.C. Vlahcevic Z.R. Hylemon P.B. Regulation of cholesterol 7α-hydroxylase expression by sterols in primary rat hepatocyte cultures.J. Lipid Res. 1995; 36: 1168-1177Google Scholar). Products were quantified by liquid scintillation counting with [3H]mevalonolactone as internal standard. Protein concentration was determined by the assay of Bradford (22Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem. 1976; 72: 248-254Google Scholar). Hepatic activities of cholesterol 7α-hydroxylase were determined by the HPLC-based assay system of Hylemon et al. (23Hylemon P.B. Studer E.J. Pandak W.M. Heuman D.M. Vlahcevic Z.R. Chiang J.Y.L. Simultaneous measurement of cholesterol 7α-hydroxylase activity by reverse-phase high performance liquid chromatography using both endogenous and exogenous [4-C]cholesterol as substrate.Anal. Biochem. 1989; 182: 212-216Google Scholar). Based on expected micellar phase and crystallization phase boundaries, supersaturated model bile systems were prepared with variable proportions of cholesterol, lecithin, and the mixtures of tauro-β-muricholate, taurocholate, and tauroursodeoxycholate in ratios of 25:75:0 (wt/wt/wt), 50:50:0 (wt/wt/wt), 85:15:0 (wt/wt/wt), and 0:20:80 (wt/wt/wt) with total lipid concentrations of 2.5 and 10 g/dl, which are similar to mouse hepatic and gallbladder biles. Model bile systems were made according to previously described methods (24Carey M.C. Small D.M. The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man.J. Clin. Invest. 1978; 61: 998-1026Google Scholar, 25Wang D.Q-H. Carey M.C. Complete mapping of crystallization pathways during cholesterol precipitation from model bile: influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems.J. Lipid Res. 1996; 37: 606-630Google Scholar) and incubated at 37°C in a waterbath. Microscopic examination for crystalline and liquid-crystalline precipitates was performed at 1-day intervals using polarizing light microscopy and phase contrast optics (Nikon, Japan). After prolonged incubation (30 days), when no further changes were observed by microscopy, two-phase (micelles and either liquid or solid cholesterol crystal-containing) and three-phase (micelles, solid, and liquid crystal-containing) zones were defined. Micellar phase boundaries of the equilibrated model bile systems were determined according to published methods (24Carey M.C. Small D.M. The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man.J. Clin. Invest. 1978; 61: 998-1026Google Scholar, 25Wang D.Q-H. Carey M.C. Complete mapping of crystallization pathways during cholesterol precipitation from model bile: influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems.J. Lipid Res. 1996; 37: 606-630Google Scholar), which were used for calculating the corrected cholesterol saturation indexes (CSI) (26Metzger A.L. Heymsfield S. Grundy S.M. The lithogenic index–a numerical expression for the relative lithogenicity of bile.Gastroenterology. 1972; 62: 499-501Google Scholar). Also, the CSI values of gallbladder and hepatic biles were calculated from the critical tables (27Carey M.C. Critical tables for calculating the cholesterol saturation of native bile.J. Lipid Res. 1978; 19: 945-955Google Scholar). Relative lipid compositions of mouse gallbladder biles were plotted on condensed phase diagrams appropriate to their mean total lipid concentrations and to their predominant bile salt compositions. Biliary phospholipids were determined as inorganic phosphorus by the method of Bartlett (28Bartlett G.R. Phosphorous assay in column chromatography.J. Biol. Chem. 1959; 234: 466-468Google Scholar). Total and individual bile salt concentrations, bile cholesterol, as well as cholesterol content in chow and gallstones were determined by HPLC (17Wang D.Q-H. Paigen B. Carey M.C. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile.J. Lipid Res. 1997; 38: 1395-1411Google Scholar). Hydrophobicity indexes of hepatic bile were calculated according to Heuman's method (29Heuman D.M. Quantitative estimation of the hydrophilic-hydrophobic balance of mixed bile salt solutions.J. Lipid Res. 1989; 30: 719-730Google Scholar). All data are expressed as means ± SD. Statistically significant differences among groups of mice fed chow or the semisynthetic diets were assessed by Student's t-test, Mann-Whitney U test, or Chi-square test. Analyses were performed with a SuperANOVA software (Abacus Concepts, Berkeley, CA). Statistical significance was defined as a two-tailed probability of less than 0.05. At week 8 of feeding, 100% (20/20) of mice fed the lithogenic diet containing 2% cholesterol and 0.5% cholic acid formed cholesterol gallstones. However, the addition of 0.5% UDCA and 0.5% β-muricholic acid to the lithogenic diet significantly (P < 0.001) decreased gallstone prevalence to 50% (10/20) and to 20% (4/20), respectively. The gallstones were usually a round and solid sphere in shape, and pale yellow to white in color. The extracted sterols from these stones contained >99% cholesterol on a dry weight basis, as determined by HPLC. The frequency distribution of gallstones displayed that 65% of mice fed the lithogenic diet formed 7–9 stones, 20% with 1–3 stones, and 15% with 4–6 stones. In mice fed the lithogenic diet plus UDCA, 40% of mice formed 1–3 stones and 10% with 4–6 stones; however, 50% of mice was gallstones free. Most notably, the majority (80%) of mice fed the lithogenic diet plus β-muricholic acid was gallstones free, as well as 20% of mice formed only 1–3 stones. Furthermore, stone size was 0.68 ± 0.27 mm in diameter in mice fed the lithogenic diet, significantly (P < 0.01) bigger than those in the UDCA group (0.36 ± 0.18 mm) and in the β-muricholic acid group (0.34 ± 0.11 mm). In addition, gallbladder values were significantly (P < 0.05) larger in mice (41 ± 17 μl) fed the lithogenic diet than those in the UDCA group (33 ± 10 μl) and in the β-muricholic acid group (30 ± 7 μl). Table 1 shows biliary lipid compositions of pooled gallbladder biles (n = 20 per group) and individual hepatic biles (n = 5 per group) at week 8 of the semisynthetic diet feeding. Mice fed the lithogenic diet displayed markedly higher mol% cholesterol, CSI value, and total lipid concentration (Table 1) compared with the mice fed the lithogenic diet plus UDCA or β-muricholic acid. Furthermore, the mean apparent CSI values and total lipid concentrations, as well as mole% cholesterol and phospholipid of hepatic biles, were significantly (P < 0.05) higher, but mole% bile salt significantly (P < 0.001) lower in the lithogenic diet-fed group compared with the lithogenic diet plus UDCA or β-muricholic acid feeding. Moreover, feeding the lithogenic diet plus β-muricholic acid and UDCA displayed significantly (P < 0.05) lower cholesterol/phospholipid and phospholipid/bile salt ratios of hepatic biles compared with the lithogenic diet (Table 1). These findings show that addition of β-muricholic acid and UDCA to the lithogenic diet mainly decreased the cholesterol and phospholipid compositions of mouse gallbladder and hepatic biles (Table 1) compared with the lithogenic diet feeding, and that solubility and phase separation of cholesterol were critically dependent on phospholipid/bile salt ratio and cholesterol concentration.TABLE 1Biliary lipid compositions of gallbladder and hepatic biles after gallstone formationaValues were determined from pooled gallbladder biles (n = 20 per group) and five hepatic biles (the first hour of biliary secretion) per group.Pooled Gallbladder BilesDietChPLBSCh/PLPL/BS[TL]CSIbThe cholesterol saturation index values of pooled gallbladder biles and individual hepatic biles were calculated from the critical tables (27), so they were estimates based on taurocholate.Corrected CSIcThe corrected cholesterol saturation index values of pooled gallbladder biles and five hepatic biles were calculated (26) based on tauro-β-muricholate and taurocholate mixture in a ratio of 25:75 (wt/wt) (Materials and Methods).mole%g/dlLD13.2218.9667.810.700.2810.311.952.41LD+UDCA7.2817.1075.620.430.239.881.201.48LD+β-MCA5.7916.9277.300.340.229.990.971.18Individual Hepatic BilesLD10.26 ± 2.4418.60 ± 1.8371.14 ± 3.880.55 ± 0.100.26 ± 0.042.64 ± 0.772.02 ± 0.302.64 ± 0.50LD+UDCA3.92 ± 0.39dP < 0.001 compared with the LD group.10.49 ± 0.84dP < 0.001 compared with the LD group.85.59 ± 0.77dP < 0.001 compared with the LD group.0.38 ± 0.06fP < 0.05 compared with the LD group.0.12 ± 0.01dP < 0.001 compared with the LD group.2.07 ± 0.371.29 ± 0.20eP < 0.01 compared with the LD group.1.73 ± 0.17eP < 0.01 compared with the LD group.LD+β-MCA4.33 ± 1.20dP < 0.001 compared with the LD group.11.49 ± 2.31dP < 0.001 compared with the LD group.84.19 ± 3.38dP < 0.001 compared with the LD group.0.39 ± 0.03fP < 0.05 compared with the LD group.0.14 ± 0.03dP < 0.001 compared with the LD group.2.64 ± 0.301.28 ± 0.17fP < 0.05 compared with the LD group.1.73 ± 0.20eP < 0.01 compared with the LD group.β-MCA, β-muricholic acid; BS, bile salts; Ch, cholesterol; CSI, cholesterol saturation index; LD, lithogenic diet containing 2% cholesterol and 0.5% cholic acid; PL, phospholipids; [TL], total lipid concentration; UDCA, ursodeoxycholic acid.a Values were determined from pooled gallbladder biles (n = 20 per group) and five hepatic biles (the first hour of biliary secretion) per group.b The cholesterol saturation index values of pooled gallbladder biles and individual hepatic biles were calculated from the critical tables (27Carey M.C. Critical tables for calculating the cholesterol saturation of native bile.J. Lipid Res. 1978; 19: 945-955Google Scholar), so they were estimates based on taurocholate.c The corrected cholesterol saturation index values of pooled gallbladder biles and five hepatic biles were calculated (26) based on tauro-β-muricholate and taurocholate mixture in a ratio of 25:75 (wt/wt) (Materials and Methods).d P < 0.001 compared with the LD group.e P < 0.01 compared with the LD group.f P < 0.05 compared with the LD group. Open table in a new tab β-MCA, β-muricholic acid; BS, bile salts; Ch, cholesterol; CSI, cholesterol saturation index; LD, lithogenic diet containing 2% cholesterol and 0.5% cholic acid; PL, phospholipids; [TL], total lipid concentration; UDCA, ursodeoxycholic acid. The HPLC analysis revealed that all bile salts were taurine conjugated and distributions of bile salt compositions were similar between hepatic and gallbladder biles. In mice fed the lithogenic diet, taurocholate (51.2 ± 4.8%), taurodeoxycholate (18.5 ± 5.5%), and taurochenodeoxycholate (18.0 ± 2.6%) were the predominant bile salt species. Tauro-β-muricholate (7.7 ± 1.5%), tauroursodeoxycholate (3.1 ± 0.5%), and tauro-ω-muricholate (1.5 ± 0.9%) were present in much smaller concentrations. In contrast, feeding the lithogenic diet plus 0.5% UDCA induced a significant (P < 0.001) increase in concentration of hydrophilic bile salts, tauro-β-muricholate (20.3 ± 1.9%), and tauroursodeoxycholate (6.0 ± 1.0%), as well as of a hydrophobic bile salt, taurochenodeoxycholate (30.2 ± 3.6%). However, there was a significant (P < 0.001) decrease in taurocholate (29.2 ± 3.7%). Moreover, no significant changes occurred in levels of tauro-ω-muricholate or taurodeoxycholate. Furthermore, mice fed the lithogenic diet plus 0.5% β-muricholic acid displayed significant (P < 0.001) increases in concentration of the hydrophilic bile salts, tauro-β-muricholate (27.6 ± 3.8%), and a significant (P < 0.001) decrease in taurochenodeoxycholate (0.9 ± 0.3%). Other bile salt compositions such as taurocholate, taurodeoxycholate, taurochenodeoxycholate, and tauro-ω-muricholate were not changed markedly compared with the lithogenic diet group. Biliary" @default.
• W2123145802 created "2016-06-24" @default.
• W2123145802 creator A5019115247 @default.
• W2123145802 creator A5044686947 @default.
• W2123145802 date "2002-11-01" @default.
• W2123145802 modified "2023-10-18" @default.
• W2123145802 title "Effect of β-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice" @default.
• W2123145802 cites W103578240 @default.
• W2123145802 cites W1436536660 @default.
• W2123145802 cites W1510622110 @default.
• W2123145802 cites W1513897103 @default.
• W2123145802 cites W1531658136 @default.
• W2123145802 cites W1664346998 @default.
• W2123145802 cites W1879942467 @default.
• W2123145802 cites W1895325632 @default.
• W2123145802 cites W1910467136 @default.
• W2123145802 cites W1929425341 @default.
• W2123145802 cites W1943976550 @default.
• W2123145802 cites W1968375829 @default.
• W2123145802 cites W1990912417 @default.
• W2123145802 cites W1997477483 @default.
• W2123145802 cites W2012675297 @default.
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• W2123145802 cites W2208529840 @default.
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