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At least 667 records · Page 37Linked to original sources
PubMed1992

Dose-dependent effects of dietary phytosterol on epithelial cell proliferation of the murine colon.

Phytosterols are a group of compounds in plants that have been found to inhibit tumour development and decrease enhanced colonic epithelial cell proliferation in carcinogen-treated rats. The mechanism by which phytosterols may inhibit tumour development and alter cell proliferation is unknown. However, studies have shown that dietary phytosterol intake may alter levels of certain promoters in the colonic lumen, leading to altered levels of colonic epithelial cell proliferation. In this study, the effect of dietary phytosterol on the proliferative status of the intestinal epithelium was investigated in mice. Inbred C57B1/6J mice were fed semi-synthetic diet (control); 0.1% cholic acid, 0% phytosterol (cholic acid control); and cholic acid plus 0.3, 1.0 or 2.0% phytosterol. Dietary cholic acid significantly increased colonic epithelial cell proliferation and the highest labelled cell position by 92 and 35%, respectively. Phytosterol significantly reduced the enhanced labelling index and the position of the highest labelled cell in a dose-dependent manner. Mitotic index was also reduced significantly by phytosterol but not in a dose-dependent manner. The results of this study indicate that phytosterol influences the colonic epithelial cell morphometrics, that are important preneoplastic events in colon carcinogenesis, and may thus contribute to a reduced risk of cancer.

Administration, Oral↗
PubMed1976

The metabolism of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid into cholic: an enzyme assay using homogenates of human liver.

An enzyme assay was developed to measure the conversion of the bile acid precursor, 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA), into cholic acid using homogenates of human liver biopsies. The average rate of metabolism of THCA into cholic acid was found to be 3.9 +/- 0.5 (+/- 1 SD) pmoles of cholic acid formed/mg liver/minute in twelve normal liver biopsies. This assay system can be used to determine if the syndrome of neonatal cholestasis associated with a metabolic block in the conversion of THCA into cholic acid is transmitted as a genetic trait.

Adolescent↗
PubMedDate not supplied

Regulation of bile acid synthesis. I. Effects of conjugated ursodeoxycholate and cholate on bile acid synthesis in chronic bile fistula rat.

Bile acid synthesis is thought to be regulated by a negative feedback mechanism which is presumably dependent upon the flux of bile acids in the enterohepatic circulation. To characterize further the role of bile acids in regulation of bile acid synthesis, we have administered pure taurine or glycine conjugates of ursodeoxycholic acid or cholic acid to chronic bile fistula rats by continuous intraduodenal infusion, thus simulating restoration of the enterohepatic circulation. The effects of these bile salt infusions on bile acid synthesis, biliary cholesterol and phospholipid secretion and on the activities of the hepatic microsomal enzymes cholesterol 7 alpha-hydroxylase and HMG-CoA reductase were evaluated. Because the rate of biliary bile salt secretion in rats with intact exteriorized enterohepatic circulation averaged 27.1 +/- 1.4 mumoles per 100 gm rat per hr, infusion rates for bile fistula studies were chosen to match (24 to 36 mumoles per 100 gm rat per hr) or exceed (48 mumoles per 100 gm rat per hr) this physiological flux. Infusion of tauroursodeoxycholic acid for 48 hr at 24 and 48 mumoles per 100 gm rat per hr failed to suppress cholic acid synthesis. Bile flow and biliary cholesterol and phospholipid secretion exhibited small, dose-dependent increases with tauroursodeoxycholic acid infusions. No suppression of cholesterol 7 alpha-hydroxylase or HMG-CoA reductase activity was observed. By contrast, taurocholic acid inhibited synthesis of chenodeoxycholate and its metabolites alpha- and beta-muricholate by 10% (NS), 66% (p less than 0.05) and 75% (p less than 0.05) at infusion rates of 24, 36 and 48 mumoles per 100 gm rat per hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Enterohepatic circulation of bile acids in infants and children with ileal resection.

Seven children who had undergone ileal resection of varying lengths as neonates were studied to determine later gastrointestinal function with specific emphasis on the enterohepatic circulation of bile acids. Fecal homogenate and aqueous supernatant bile acid concentrations and serum bile acids were analyzed. Cholic acid kinetics were measured by the isotopic dilution technique, with multiple duodenal bile samples obtained within 48 hr after intravenous 14C--cholic acid. As compared to those of age-matched controls, significantly increased fecal homogenate bile acid concentrations (p less than 0.05) and fecal aqueous supernatant bile acid concentrations (p less than 0.01) were present. Fasting and postcibal serum bile acid concentrations were significantly reduced (p less than 0.001). Increased FTRs for cholic acid (p less than 0.001) were present in children with resection. The FTR correlated significantly with resection length (p = 0.012). Fasting pool sizes of chenodeoxycholic and cholic acid measured after an overnight fast were variable. Three children had significantly reduced cholic acid and chenodeoxycholic acid pools, and one had a reduction in the cholic acid pool only. The cholic acid pool size correlated directly with the postprandial rise in serum CG concentration (p = 0.003). The fecal coefficient of fat excretion and fecal weights were only moderately increased. Although rapid turnover of bile acids was present following neonatal ileal resection, efficient compensatory mechanisms during infancy and childhood allowed adequate intraluminal bile salt concentrations for normal fat solubilization throughout the day and resultant mild steatorrhea and diarrhea in our study patients.

Bile Acids and Salts↗
PubMed1995

The role of sodium in the uptake of ursodeoxycholic acid in isolated hamster hepatocytes.

The uptake of ursodeoxycholic acid (UDCA) was studied in isolated hamster hepatocytes. The uptake was rapid and linear up to 60 seconds for each concentration studied. When the uptake rate was plotted against UDCA concentration, the curve was nonlinear, indicating both saturable and nonsaturable uptake mechanisms. The nonsaturable process had a diffusion constant of 0.01 nmol.s-1.g of cell.mumol/L-1. The saturable component was characterized by a maximum rate of uptake (Vmax) of 5.68 nmol.s-1.g of cell-1 and a Michaelis constant (Km) of 224 mumol/L. In the presence of monensin, ouabain, and amiloride, the uptake of UDCA was significantly decreased by 35% to 55%, whereas the sodium-independent uptake of UDCA was not affected by either monensin or amiloride, thereby confirming sodium dependence of UDCA uptake. The sodium-dependent uptake of UDCA was characterized by a Vmax and a Km of 1.57 nmol.s-1.g of cell-1 and 46 mumol/L, respectively. The rate of uptake of UDCA was maximal at extracellular sodium concentrations > or = 20 mmol/L. Furthermore, the uptake of UDCA was competitively inhibited by both taurocholic acid and cholic acid with an inhibitory constant (Ki) of 60 mumol/L and 48 mumol/L, respectively. Finally, 1 mmol/L of 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) inhibited solely the sodium-dependent uptake of cholic acid and UDCA. These findings confirm that the hepatocellular uptake of UDCA involves, at least in part, a sodium-dependent, ouabain, amiloride, and DIDS-sensitive transporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Direct measurement of first-pass ileal clearance of a bile acid in humans.

The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%), implying a possible wide variation in recycling frequency per day.

Adult↗
PubMed1984

Specificity of bile salt sulfatase activity in man, mouse and rat intestinal microflora.

Desulfation of bile acid 3-, 7- and 12-monosulfates was studied in incubates of fecal flora of man, rat and mouse. In anaerobic incubates, the 3 alpha-sulfates of the 5 beta-bile acids chenodeoxycholic acid and cholic acid, as well as the 3 alpha-sulfate of the 5 alpha-bile acid allochenodeoxycholic acid, were desulfated and further metabolized with the formation of a variety of metabolites. Desulfation yields were low in aerobically incubated samples, and aerobic subcultures were always negative. The 7- or 12-monosulfate esters of chenodeoxycholic acid and cholic acid were not hydrolyzed, neither anaerobically nor aerobically. High numbers (10(7) per 10(9) total count) of bile salt 3-sulfatase producing bacteria were present in rat cecal contents. No desulfating bacteria were detected in the proximal or medium small intestine of the rat, whereas low numbers were found in 2 out of 5 samples from the distal small intestine. These results reflect the predominantly anaerobic character of the bile salt sulfatase producing microflora in the intestine and suggest that the intestinal microflora of man, rat and mouse do not possess bile salt 7- or 12-sulfatase activity.

Anaerobiosis↗
PubMedDate not supplied

Bile acid profiles in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis.

Bile acid profiles of bile, urine, and feces obtained from a patient with cerebrotendinous xanthomatosis on the same day have been analyzed by gas-liquid chromatography-mass spectrometry after fractionation into groups by mode of conjugation by an ion-exchange chromatography. The predominant biliary bile acid was cholic acid conjugated with glycine and taurine. Lesser amounts of the amino acid conjugates of chenodeoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid, allocholic acid, and deoxycholic acid, and of unconjugated norcholic acid and allonorcholic acid were also present in the bile. The major fecal bile acid was 7-epicholic acid. Relatively large amounts of bile acids were excreted in the urine. Unconjugated 7-epicholic acid, norcholic acid, allonorcholic acid, and cholic acid predominated. The bile acid profiles of the patient were different from those of normal subjects and should be useful for the diagnosis.

Bile↗
PubMed1987

Impaired polymorphonuclear leukocyte function in biliary atresia: role of bilirubin and bile acids.

Our previous study suggested that impaired bactericidal activity of polymorphonuclear leukocytes in patients with biliary atresia might be due to decrease in superoxide-generating activity and that serum factors may play an important role. In the present study, analysis of the patients' serum revealed that, among 15 bile acids, glycine or taurine conjugated chenodeoxycholic acid and cholic acid were markedly elevated. To examine the effects of bilirubin and these bile acids and conjugated lithocholic acids on the leukocyte function, we measured cytolysis, phorbol myristate acetate-induced superoxide generation, and myeloperoxidase activity, using normal human polymorphonuclear leukocytes. Bilirubin ranging from 5 to 20 mumol/L was cytolytic and more potently inhibited the superoxide generation. The inhibition by bilirubin was also observed in the presence of 10% human serum or 2.0% human serum albumin, though the cell viability was almost completely preserved. On the other hand, conjugated chenodeoxycholic acids and cholic acids, ranging from 0.5 to 1.5 mmol/L or conjugated lithocholic acids, ranging from 0.02 to 0.05 mmol/L, did not inhibit the superoxide generating activity, though the conjugated chenodeoxycholic acids and lithocholic acids did induce cytolysis. Myeloperoxidase activity was little affected, except in the case of conjugated lithocholic acids. These results suggest that in patients with biliary atresia, bilirubin, probably the unconjugated form, more than bile acids might be one of the influential factors in the suppression of bactericidal activity of polymorphonuclear leukocytes, by inhibiting the superoxide-generating activity.

Bile Acids and Salts↗
PubMed1979

Defects of bile acid synthesis in Zellweger's syndrome.

Abnormal mitochondrial structure and function have been documented in patients with Zellweger's syndrome (cerebrohepatorenal syndrome). In vitro studies have suggested that the formation of C24 bile acids (chenodeoxycholic acid and cholic acid) from C27 cholesterol requires mitochondrial oxidative clevage of the terminal three carbons of the side chain. Therefore, three patients with Zellweger's syndrome were examined for the presence of mitochondrial defects in bile acid synthesis. All three excreted excessive amounts of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oicacid, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid, and 3 alpha, 7 alpha, 12 alpha, 24 xi-tetrahydroxy-5 beta-cholestan-26-oic acid (varanic acid), precursors of chenodeoxycholic acid and cholic acid that have undergone only partial side chain oxidation. These findings give added support to the role of mitochondrial oxidative side chain cleavage in the overall scheme of bile acid synthesis.

Bile Acids and Salts↗
PubMed1973

Bile acids in the diarrhoea of ileal resection.

Twenty individual diarrhoeal stools from three patients with ileal resection were centrifuged at 14 000 g for one hour at 10 degrees C to separate the stool into pellet and supernatant. Bile acids and electrolytes were measured in each phase. Relationships were examined between chenodeoxycholic acid and cholic acid in each phase and in toto to electrolyte and water loss. Chenodeoxycholic acid was associated with electrolyte and water loss whether present in solid or liquid phase. The association varied between individuals. The cholic acid content of the stool showed no association with electrolyte and water loss. It would appear that it is the total amount of chenodeoxycholic acid entering the colon, irrespective of its physical state, that is important in the diarrhoea of ileal dysfunction.

Adult↗
PubMed1993

Comparative binding of bile acids to serum lipoproteins and albumin.

Characteristics of the binding of lithocholic acid (LC), chenodeoxycholic acid (CDC), and cholic acid to human plasma proteins were studied. Affinity of the different plasma protein fractions for the bile acids studied decreased with increased polarity of the steroid nucleus of the bile acid. Binding of LC, CDC, and cholic acid to the lipoprotein-free, albumin-rich plasma fraction was characterized by two classes of binding sites with respective KDs of 2, 5, and 51 microM, and of 39, 2,387, and 5,575 microM, while corresponding Bmax values were similar for the different bile acids, at around 6 and 100 nmol/mg protein. Bile acid binding to the different lipoprotein fractions was characterized by a single population of binding sites, with a KD ranging from 47 to 66 microM for LC, 695 to 1010 microM for CDC, and 2,511 to 2,562 microM for cholic acid. Bmax values, at 416-913 nmol/mg protein, were similar among the different bile acids studied. Both glycine- and taurine-conjugated, as well as unconjugated LC competitively inhibited [24-14C]LC binding to low density (LDL) and to high density lipoproteins (HDL) to the same extent, while the more polar LC-3-sulfate, CDC, and cholic acid were increasingly less potent in displacing LC binding from the respective lipoproteins. Furthermore, all bile acids studied shared the same lipoprotein binding site. The lipoprotein fluorescence at 330-334 nm, following excitation at 280 nm, was diminished after incubation with LC, suggesting that the bile acid masks the tryptophan residues of the protein moiety. Finally, the initial rate of uptake of 1 microM LC, in isolated hamster hepatocytes, at around 0.045 nmol.sec-1.mg cell wt-1, was not affected by the protein carrier. However, for the same concentration of LC, bound to either LDL or HDL, LC binding resulted in 75-77% of the total [24-14C]LC nonspecifically bound to the hepatocyte, compared to 65% when bound to albumin, and 45% in the absence of protein. The studies show that, under conditions when the serum bile acid concentration exceeds the capacity of the high affinity class of albumin binding sites for bile acids, lipoproteins have similar or greater affinity to bind bile acids than does albumin. The ability of lipoproteins to increase the nonspecific association of lithocholic acid with liver cells may also facilitate bile acid association with extrahepatic tissues. As lipoproteins, in contrast to albumin, are targeted to most cells, they may play a major role in the transport of potentially toxic bile acids to peripheral cells.

Animals↗
PubMed2006

Photovoltaic conversion using Zn chlorophyll derivative assembled in hydrophobic domain onto nanocrystalline TiO2 electrode.

Photovoltaic conversion using zinc chlorin-e6 (ZnChl-e6), which is zinc chlorophyll-a derivative, and fatty acid (myristic acid or cholic acid) co-adsorbed nanocrystalline TiO2 layer onto ITO glass (OTE) electrode is developed. The maximum peaks of photocurrent action spectrum of the ZnChl-e6 adsorbed TiO2 layer onto OTE (ZnChl-e6/TiO2) are 400, 660 and 800 nm, respectively. Especially the IPCE value at 800 nm (7.5%) is larger than that of 660 nm (6.9%). This result indicates that ZnChl-e6 molecules is aggregated or formed dimer on a nanocrystalline TiO2 layer onto OTE and the absorption band is shifted to near IR region. The photocurrent action spectrum of ZnChl-e6 and cholic acid adsorbed TiO2 layer onto OTE (ZnChl-e6-Cho/TiO2 is similar to that of the UV-vis absorption spectrum in methanol solution, and IPCE values at 400 and 660 nm (8.1%) increase and the IPCE value at 800 nm (4.1%) decreases, indicating that the aggregation of ZnChl-e6 molecules on the TiO2 is suppressed by cholic acid. By using ZnChl-e6-Cho/TiO2, the short-circuit photocurrent density and open-circuit photovoltage also increase compared with that of ZnChl-e6 adsorbed nanocrystalline TiO2 electrode.

Chlorophyll↗
PubMed1986

Gas chromatography-mass spectrometry of isobutyl ester trimethylsilyl ether derivatives of bile acids and application to the study of bile sterol and bile acid biosynthesis in rat liver epithelial cell lines.

The derivatization of bile acids into trimethylsilyl ether isobutyl ester (IBTMS) and of neutral sterols into trimethylsilyl ether (TMS) allowed the separation on an OV-1 capillary gas chromatography column of 15 bile steroids as follows: cholesterol, 7 alpha-hydroxycholesterol, 6 beta-hydroxycholesterol, 6 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, lithocholate, deoxycholate, 25-hydroxycholesterol, chenodeoxycholate, cholate, murocholate, hyodeoxycholate, ursodeoxycholate, hyocholate, and beta-muricholate. Fragmentation data of the coupled gas chromatographic-mass spectrometric (GC-MS) analysis of these nine bile acids as IBTMS derivatives under electron impact and chemical ionizations (methane, isobutane, and ammonia) are given. The ammonia chemical ionization appears to be the best mode for compound identification and quantitation due to fragmentations into high mass ions. The comparison of methylene units of the five sterols as TMS derivatives and of each type of methyl, TMS, or isobutyl ester of the nine bile acids as TMS ethers showed that isobutyl esterification increased dramatically the retention time of the bile acids, allowing their separation after the neutral sterols. Different methods of GC-MS analysis were applied to the study of bile steroid secretion in long-term rat liver epithelial cell lines, either serum-supplemented cell lines or serum-free cell lines, growing in serum-free medium since the primary explanation or after adaptation of serum-supplemented lines to this medium. It is demonstrated for the first time that liver epithelial cell lines maintain the metabolic pathway leading from synthesized cholesterol to dioxygenated sterols and the two normal main primary bile acids of the liver, chenodeoxycholic acid and cholic acid, up to 32-47% of the in vivo daily rate, and in addition the production of alpha-muricholic acid, the bile acid marker of murine liver.

Animals↗
PubMed1996

Effects of bile acids on iodide uptake and deoxyribonucleic acid synthesis in porcine thyroid cells in primary culture.

The effects of bile acids on iodide uptake and DNA synthesis were studied in cultured porcine thyroid cells. All five bile acids, which are commonly found in serum, chenodeoxycholic acid (CDCA), cholic acid (CA), deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) dose-dependently inhibited both basal and TSH-induced iodide uptake at concentrations of 25-250 microM. Since CDCA is one of the two major primary endogenous bile acids, were studied mainly the effects of CDCA. The inhibitory effect of CDCA was detected after 24 h treatment of thyroid cells, and was dependent on the time of exposure up to 72 h. Treatment of thyroid cells with CDCA for 72 h inhibited cAMP production stimulated by 50 mU/L TSH or 0.5 mg/L forskolin and also inhibited iodide uptake induced by 0.5 mM 8-bromo cAMP or 0.5 mg/L forskolin. These results suggest that CDCA inhibits iodide uptake by decreasing cAMP production as well as post-cAMP generation. Bile acids except LCA stimulated [3H]thymidine incorporation into the thyroid cells by itself, indicating that the inhibitory effect of bile acids on iodide uptake is not due to cytotoxic effect. In conclusion, these findings suggest that the direct inhibition of thyroid function by bile acids might cause hypothyroidism in chronic liver disease.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1980

An in vivo evaluation of the quantitative significance of several potential pathways to cholic and chenodeoxycholic acids from cholesterol in man.

The present study was designed to obtain more definitive information in man on the metabolic pathways to chenodeoxycholic acid and to cholic acid via a pathway not involving an initial 7 alpha-hydroxylation of cholesterol. Four bile fistula patients were administered consecutively two or more of the following 3H-labeled bile acid intermediates: 7 alpha-hydroxycholesterol, 7 alpha-hydroxy-4-cholesten-3-one, 5 beta-cholestane 3 alpha,7 alpha,26-triol, 26-hydroxycholesterol,7 alpha,26-dihydroxy-4-cholesten-3-one, and 5-cholestene-3 beta,12 alpha-diol. Both 7 alpha-hydroxy[7 beta-3H]cholesterol and 7 alpha-hydroxy-4-[6 beta-3H]cholesten-3-one were efficiently converted to bile acids and preferred chenodeoxycholic acid over cholic acid. The specific activity time curves indicated that a portion of cholic acid synthesis did not pass through 7 alpha-hydroxycholesterol. [3H]26-Hydroxycholesterol and [3H]-5-cholestene 3 beta,12 alpha-diol, two potential intermediates of this bypass pathway to cholic acid, were poorly converted to primary bile acids (10 to 27%). The [3H]26-hydroxycholesterol preferred chenodeoxycholic over cholic acid by about 4 to 1. The [3H]5-cholestene 3 beta,12 alpha-diol formed cholic acid in low yield (10 to 20%). It is concluded that pathways to primary acids from cholesterol through 26-hydroxycholesterol and 5-cholestene 3 beta,12 alpha-diol are probably of minor quantitative significance. A selective pathway to chenodeoxycholic acid via 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one was also investigated. The 5 beta-cholestane 3 alpha,7 alpha,26-triol was converted in about equal amounts to cholic and chenodeoxycholic acids. The 7 alpha-hydroxy-4-cholesten-3-one was also efficiently converted to both bile acids but preferred chemodeoxycholic acid. The most efficient precursor of chenodeoxycholic acid was 7 alpha,26-dihydroxy-4-cholesten-3-one, which was efficiently converted to primary bile acids; chenodeoxycholic acid was preferred over cholic acid by approximately 7 to 1. These findings suggest the presence of a major pathway to chenodeoxycholic acid via the 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one and intermediate formation of 7 alpha,26-dihydroxy-4-cholesten-3-one.

Bile↗