SEARCH · PubMed Health

Results for “CHOLIC ACID”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed1981

Cholesterol absorption in cirrhosis: the role of total and individual bile acid pool size.

Dietary cholesterol absorption was studied in patients with either "mild" (n = 23) or "severe" (n = 12) liver cirrhosis in relation to both total and individual bile acid pool size. Cholesterol absorption was significantly reduced in both groups of patients, and it was inversely related (r = -0.68; p less than 0.001) to the severity of the disease. Total, cholic acid, and deoxycholic acid p ool sizes were significantly reduced in cirrhosis, and a correlation was found between cholesterol absorption and cholic acid pool size (r = 0.78; p less than 0.001). In 5 patients, cholesterol absorption and bile acid pool size were estimated both before and after treatment with cholic acid (15 mg/kg/day) plus ampicillin (2 g/day). The treatment was followed by a mean threefold increase of cholic acid pool and by a sharp enhancement of cholesterol absorption in each patient. In conclusion, cholesterol absorption is often impaired in cirrhosis and is related to the severity of the disease. The correlation between cholic acid pool and cholesterol absorption and the constant increase of the absorption values after cholic acid pool expansion suggest that the size of cholic acid pool may be considered as an important factor in the regulation of cholesterol absorption.

Adult↗

PubMed1982

Factors controlling the concentrations of methotrexate in cultured hepatic cells.

The polyglutamate metabolites of methotrexate are as inhibitory to the target enzyme dihydrofolate reductase as is methotrexate. Because of their greater retention they have a longer half-life within the cells and thus a greater potential for cytotoxicity. These metabolites have been found in numerous cells and tissues and are extensively synthesized in cultured hepatic cells. Uptake of methotrexate by primary cultures of rat hepatocytes occurs by a pathway which is independent of the folate coenzymes but appears to be related in some way to cholic acid and organic anion uptake. The evidence for the commonality of these pathways is (a) an instability of both uptake systems in the absence of hormones in the culture medium, (b) nearly equal inhibition of uptake by PCMS and NEM, and (c) cross competition of cholic acid and methotrexate for entry into the cells. Cholic acid and BSP can also selectively inhibit methotrexate polyglutamate formation in hepatocytes. Methotrexate entry into H35 hepatoma cells is mediated by the transport system which is shared by folate coenzymes and is not inhibited by cholic acid, BSP or sulfhydryl reagents. At concentrations of cholic acid or BSP which inhibit methotrexate polyglutamate formation in hepatocytes there is little or no loss of polyglutamate formation in H35 cells, possibly because BSP and cholic acid are taken up less by H35 cells than by hepatocytes.

Animals↗

PubMed1993

Effect of dietary n-3 versus n-6 polyunsaturated fatty acids on hepatic excretion of cholesterol in the hamster.

Dietary polyunsaturated fatty acids of the n-6 and the n-3 class show differing effects on serum lipids and hepatic lipoprotein metabolism, which could be induced by alterations in hepatocellular cholesterol balance. As both fatty acid classes exert parallel effects on lipoprotein uptake and synthesis of cholesterol in the liver, we studied whether they have differing effects on the excretory pathways for cholesterol. Male Syrian hamsters were fed for 3 weeks low-cholesterol diets supplemented (9% w/w) with either saturated (coconut fat), n-6 unsaturated (safflower oil) or n-3 unsaturated fatty acids (fish oil), which shifted the serum lipid levels. N-6 unsaturated fatty acids increased both the synthesis of cholic acid (+57%; P = 0.05) and, in fistula bile, the secretion of cholesterol (+37%; P < 0.05 vs. saturated fatty acids). By contrast, n-3 unsaturated fatty acids did not enhance synthesis of cholic acid or biliary secretion of cholesterol (-30%, NS). The fatty acid pattern of biliary phospholipids was modified according to the major unsaturated fatty acids in the diet. The alterations both in phospholipid fatty acid composition and in secretory ratio of cholesterol to phospholipids and bile acids persisted during controlled secretion of taurocholic acid at increasing rates. In conclusion, hepatic excretion of cholesterol is increased on dietary n-6 unsaturated fatty acids, and low on n-3 unsaturated fatty acids. These two dietary fatty acid classes change differently the fatty acid composition of biliary phospholipids and the secretory ratio of cholesterol to phospholipids and bile acids in bile.

Animals↗

PubMed1983

Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study.

On the basis of different in vitro studies, we have previously suggested that the basic metabolic defect in the rare inherited disease cerebrotendinous xanthomatosis (CTX) is a lack of a hepatic mitochondrial C27-steroid 26-hydroxylase, involved in the normal biosynthesis of bile acids (1980. J. Clin. Invest. 65: 1418-1430; 1981. J. Lipid Res. 22: 191-200; 22: 632-640). In the present work, this hypothesis was tested in vivo. One patient with CTX and two control subjects received intravenously a mixture of [4-14C]7 alpha-hydroxy-4-cholesten-3-one and [6 beta-3H]7 alpha,26-dihydroxy-4-cholesten-3-one, steroids believed to be important precursors of chenodeoxycholic acid. The ratio between 14C and 3H in cholic acid and chenodeoxycholic acid isolated from bile of the CTX-patient was approximately 1/40 and 1/60 of those of the control subjects, respectively. Another patient with CTX and one control subject received a mixture of [4-14C]5 beta-cholestane-3 alpha,7 alpha-diol and [1,2-3H]5 beta-cholestane-3 alpha,7 alpha,26-triol, both possible precursors to chenodeoxycholic acid. In this case the 14C/3H ratio in cholic acid and chenodeoxycholic acid from the patient with CTX was 1/10 and 1/15, respectively, compared with that of the control subject. The most likely explanation for these findings is that very little of the 14C-precursors, i.e. without a 26-hydroxyl group, can be converted into cholic acid and chenodeoxycholic acid because of a defect of the 26-hydroxylase step. The results obtained are in accord with our previous findings in vitro. The results further underline the importance of the 26-hydroxylase pathway in the normal biosynthesis of cholic acid and chenodeoxycholic acid in man.

Adult↗

PubMed1990

Potential bile acid precursors in plasma--possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man.

The plasma concentrations of 3 beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid have been compared with that of 7 alpha-hydroxy-4-cholesten-3-one in healthy subjects and in patients with an expected decrease or increase of the bile acid production. In controls and patients with liver disease, the level of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid was positively correlated to that of 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and not to that of 7 alpha-hydroxy-4-cholesten-3-one. In patients with stimulated bile acid formation the levels of the acids were not correlated to each other but there was a significant positive correlation between the levels of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid and 7 alpha-hydroxy-4-cholesten-3-one. These findings indicate that the precursor of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid differs depending on the activity of cholesterol 7 alpha-hydroxylase. Since the activity of this enzyme is reflected by the level of 7 alpha-hydroxy-4-cholesten-3-one in plasma the findings are compatible with a formation of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid from 3 beta,7 alpha-dihydroxy-5-cholestenoic acid when the rate of bile acid formation is normal or reduced and from 7 alpha-hydroxy-4-cholesten-3-one under conditions of increased bile acid synthesis. In support of this interpretation, 7 alpha,26-dihydroxy-4-cholesten-3-one was identified at elevated levels in plasma from patients with ileal resection or treated with cholestyramine. The levels of 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one were also higher than normal in these patients. Based on these findings and previous knowledge, a model is proposed for the biosynthesis of bile acids in man. Under normal conditions, two major pathways, one "neutral" and one "acidic" or "26-oxygenated", lead to the formation of cholic acid and chenodeoxycholic acid, respectively. These pathways are separately regulated. When the activity of cholesterol 7 alpha-hydroxylase is high, the "neutral" pathway is most important whereas the reverse is true when cholesterol 7 alpha-hydroxylase activity is low. In cases with enhanced activity of cholesterol 7 alpha-hydroxylase, the "neutral" pathway is connected to the "acidic" pathway via 7 alpha,26-dihydroxy-4-cholesten-3-one, whereas a flow from the acidic pathway to cholic acid appears to be of minor importance.

Adult↗

PubMed2003

Cholic acid-carboplatin compounds (CarboChAPt) as models for specific drug delivery: synthesis of novel carboplatin analogous derivatives and comparison of the cytotoxic properties with corresponding cisplatin compounds.

This report continues our work on new compounds which consist of three functional parts--a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt-Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], [diamine=CholCOO(CH(2))(n)CH(CH(2)NH(2))(2) and THP(CH(2))(n)CH-(CH(2)NH(2))(2), n=4, 6, 8, 11]. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue.

Antineoplastic Agents↗

PubMed1977

Effect of estradiol-17beta on the metabolism of bile acids in the rat.

The effect of estradiol-17beta on the metabolism of bile acids has been studied in male rats. 1. A 3-day acute treatment with 100 microgram/100 g body weight of the hormone caused a decrease in serum cholesterole and an increase in hepatic cholesterol. A chronic treatment with the same quantity twice a week for 3 weeks induced hypercholesteremia, which continued for 10 days after the final dosage, but there was no change in hepatic total cholesterol. 2. Fistula bile of both groups of treated rats collected during 30 min was analyzed for bile acid components. Hyodeoxycholic acid and/or chenodeoxycholic acid increased relative to cholic acid in both groups, as compared with the controls. 3. Kinetic study of the metabolism of bile acids in the chronically treated rats revealed a more than twofold enlargement of the pool size but an almost unchanged half-life of chenodeoxycholic acid. As for cholic acid, essentially no change in pool size or half-life was observed. 4. These results indicate that chronic treatment of male rats with estradiol-17beta causes an increase in elimination of hepatic cholesterol via the bile acid pathway.

Animals↗

PubMed1978

Bile acid pattern in human amniotic fluid.

Individual bile acids were determined in twenty-nine amniotic fluid specimens obtained from twenty-six women between the 32nd and 41st week of gestation. Total bile acid concentration ranged from 0.4 to 4.8 mumol/l with a mean of 1.57 mumol/l. Besides the two major bile acids of man, cholic acid and chenodeoxycholic acid, 3beta-hydroxy-5-cholenoic acid was found in all, lithocholic acid in ten and deoxycholic acid in nine of the twenty-nine amniotic fluid samples. 3beta-Hydroxy-5-cholenoic acid averaged 39.8% of total bile acids during 32-37 weeks of gestation and 20.2% at term (P less than 0.01). These findings point towards important differences between fetal and adult bile metabolism and may reflect maturation of hepatic bile acid biosynthesis near term.

Amniotic Fluid↗

PubMed1978

Serum bile acids in patients with viral hepatitis.

Total and individual serum bile acid concentrations were studied in 18 patients with viral hepatitis. The initial high values returned to the normal range at approximately the same time as the conventional liver function tests. Chenodeoxycholic acid was the predominant bile acid initially, but cholic acid predominated as the disease resolved. All patients had proportionately less doexycholic acid than controls. It is concluded that the measurement of serum bile acid does not provide added information of value in the management of patients with viral hepatitis.

Bile Acids and Salts↗

PubMed1987

Enzymes involved in the formation of 3 beta, 7 beta-dihydroxy-12-oxo-5 beta-cholanic acid from dehydrocholic acid by Ruminococcus sp. obtained from human intestine.

Ruminococcus sp. PO1-3 from human intestinal flora reduced dehydrocholic acid to 3 beta-hydroxy-7,12-dioxo-5 beta-cholanic acid by means of the enzyme 3 beta-hydroxysteroid dehydrogenase (Akao, T., Akao, T., Hattori, M., Namba, T. and Kobashi, K. (1986) J. Biochem. (Tokyo) 99, 1425-1431). This bacterium and its crude extract gave rise to another product, showing a lower RF value on TLC, from dehydrocholic acid. The product was identified as 3 beta, 7 beta-dihydroxy-12-oxo-5 beta-cholanic acid. The crude extract reduced 7-ketolithocholic acid and its methyl ester, but not 6-ketolithocholic acid and 12-ketochenodeoxycholic acid, in the presence of NADPH, and oxidized ursodeoxycholic acid and beta-muricholic acid, but not cholic acid, chenodeoxycholic acid, deoxycholic acid and hydrocholic acid, in the presence of NADP+. Therefore, besides 3 beta-hydroxysteroid dehydrogenase, 7 beta-hydroxysteroid dehydrogenase was shown to be present in this bacterium. The two dehydrogenases were clearly separated from each other by butyl-Toyopearl 650 M column chromatography. From dehydrocholic acid, 7 beta-hydroxy-3,12-dioxo-5 beta-cholanic acid was produced by 7 beta-hydroxysteroid dehydrogenase and 3 beta, 7 beta-dihydroxy-12-oxo-5 beta-cholanic acid was produced by combination of two enzymes, 7 beta- and 3 beta-hydroxysteroid dehydrogenase.

3-Hydroxysteroid Dehydrogenases↗

PubMed1980

Serum lipids, biliary lipid composition, and bile acid metabolism in vegetarians as compared to normal controls.

Since dietary factors have been implicated in various diseases, such as coronary heart disease, gallstone formation and colonic cancer, possibly by affecting cholesterol and bile acid metabolism, we studied serum lipid levels, biliary lipid composition, cholic acid and deoxycholic acid kinetics in a group of young healthy male vegetarians and in age, sex and weight matched control subjects. Daily intake of nutrients was higher with respect to polyunsaturated fatty acids, carbohydrates and dietary fibre in the vegetarian group. Although mean serum lipid levels in the vegetarian were 8-28% lower than in the control subjects, differences were not statistically significant. Biliary lipid and biliary bile acid composition were similar in both groups. Bile acid kinetics, measured after simultaneous injection of [3H]cholic acid and [14C]deoxycholic acid, showed a slightly lower output of cholic acid and a slightly higher input of deoxycholic acid in the vegetarians, this causing a significantly (P less than 0.025) higher 7 alpha-dehydroxylation fraction (input deoxycholic acid divided by synthesis of cholic acid) in the vegetarians. Our results in young males suggest that bile acid conservation is associated with a vegetarian diet, but do not support the supposition that a vegetarian diet reduces deoxycholate formation.

Adult↗

PubMed1995

Absence of correlation between hepatic function and characteristics of migrating motor complexes in the gastrointestinal tract.

BACKGROUND: Cyclic changes in gallbladder filling and emptying during the migrating motor complex (MMC) cycle have been demonstrated by scintigraphy. However, a possible cyclic change in the hepatic function and handling of the pharmacologic agents used for scintigraphy during the MMC cycle could have an influence on these results. The aim of the present study was to investigate the hepatic handling of cholic acid and mebrofenin in relation to the MMCs of the gastrointestinal tract. METHODS: The plasma disappearance rate of 14C-cholic acid and the hepatic uptake and excretion of 99mTc-mebrofenin were examined during phase I and phase II of the MMC in six healthy male volunteers. RESULTS: The plasma disappearance rate of 14C-cholic acid showed a biexponential course with an initial rapid and late slow phase after a bolus injection. There were no significant differences between the initial or late plasma disappearance rate of 14C-cholic acid during phase I as compared with phase II. The results of the time-activity curves from the 99mTc-mebrofenin scintigraphy showed an exponential rapid increase in radioactivity followed by an almost linear slow decrease after a bolus injection. There was no significant difference between phase I and phase II in any of the variables studied. CONCLUSION: The lack of a relationship between hepatic handling of cholic acid and mebrofenin and MMC excludes this as a possible source of error in the investigations of the dynamic function of the enterohepatic circulation and especially gallbladder motility by the use of either cholic acids or iminodiacetic acid derivatives as investigative agents.

Adult↗

PubMed1981

Plasma bile acid levels and liver disease.

The plasma cholic acid, chenodesoxycholic acid and desoxycholic acid levels were studied by spectrofluoremetry in 153 cases. The values of 67 controls with no evidence of hepatobiliary or intestinal disease were compared with those of 86 patients with liver and biliary tract disease. The fasting values failed to provide more diagnostic information than did conventional laboratory assays. Plasma bile acid concentrations exceeding 2.5 mu mol/l are conclusive of liver or biliary disease. A cholic acid/chenodesoxycholic acid quotient higher than 1.0 is a sign of cholestasis. Estimation of bile acids after food intake was found more informative. The plasma cholic acid- and chenodesoxycholic acid levels underwent a considerable increase 1 to 2 hours after meals. A more marked increase of chenodesoxycholic acid than of cholic acid (the ratio of the two being in excess of 1.0) is indicative of cholestasis and is most marked in primary biliary cirrhosis.

Bile Acids and Salts↗

PubMed1979

Metabolism of potential precursors of chenodeoxycholic acid in cerebrotendinous xanthomatosis (CTX).

In patients with cerebrotendinous xanthomatosis (CTX), diminished cholic acid production is associated with incomplete oxidation of the cholesterol side chain and the excretion of C(25)-hydroxy bile alcohols. The aims of this investigation were 1) to provide quantitative information on the pool size and production rate of chenodeoxycholic acid by the isotope dilution technique; and 2) to investigate the possible existence of a block in chenodeoxycholic acid synthesis and explain the absence of chenodeoxycholic acid precursors in CTX. After the injection of [24-(14)C]chenodeoxycholic acid, measurements of chenodeoxycholic acid pool size and production rate in a CTX subject were, respectively, 1/20 and 1/6 as great as controls. Further, three potential precursors of chenodeoxycholic acid, namely [G-(3)H]7alpha-hydroxy-4-cholesten-3-one, [G-(3)H]5beta-cholestane-3alpha,7alpha,25-triol, and [G-(3)H]5beta-cholestane-3alpha,7alpha,26-triol, were administered to the CTX and control subjects and the specific activity curves of [G-(3)H]cholic acid and [G-(3)H]chenodeoxycholic acid were constructed and compared. In the control subjects, the two bile acids decayed exponentially, but in the CTX patient maximum specific activities were abnormally delayed, indicating the hindered transformation of precursor into bile acid. These results show that chenodeoxycholic acid synthesis is small in CTX and that the conversion of 7alpha-hydroxy-4-cholesten-3-one, 5beta-cholestane-3alpha,7alpha,25-triol, and 5beta-cholestane-3alpha,7alpha,26-triol to both chenodeoxycholic acid and cholic acid were similarly impaired.

Adult↗

PubMed1979

Effect of coprophagy on bile acid metabolism in the rabbit.

The effect of coprophagy on the 7 alpha-dehydroxylation of biliary bile acids was studied in the rabbit. Bile acid composition of bile and intestinal contents was analyzed by gas-liquid chromatography and thin layer chromatography. Biliary bile acid composition of normal rabbits (n = 5) was: deoxycholic acid, 95.3 +/- 1.0SE % and cholic acid, 2.3 +/- 1.1SE %. When coprophagy was prevented, significant alterations were observed in biliary bile acid composition, including a considerable decrease in deoxycholic acid (82.5 +/- 2.8SE %, p less than 0.01) and a marked increase in cholic acid (15.2 +/- 3.0SE %, p less than 0.002). These results indicate that coprophagy is a factor causing an increase of the 7 alpha-dehydroxylated bile acid, deoxycholic acid (and lithocholic acid when the animals were fed chenodeoxycholic acid) in rabbit bile.

Animals↗

PubMed1989

Bile acid metabolism in human hyperthyroidism.

Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry. Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 +/- 33 vs. 261 +/- 51 mg per dl, p less than 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 +/- 2.8 vs. 7.9 +/- 4.2 mu moles per kg per day, p less than 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 +/- 3.4 vs. 22.0 +/- 5.2 mu moles per kg, p less than 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum. The depression of cholic acid synthesis in the presence of unaltered subjects is compatible with an inhibition of hepatic 12 alpha-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.

Aged↗

PubMed2005

Cholic acid-derived facial amphiphiles with different ionic characteristics.

A cholate derivative with three epoxide groups was synthesized from cholic acid by allylation followed by epoxidation. Ring opening of the epoxides by various nucleophiles yielded facial amphiphiles with anionic, cationic, or nonionic functional groups. The critical micelle concentrations of these amphiphiles largely depend on the number of charged groups on the molecule. A facial amphiphile with pH-tunable micellization was prepared. Its aggregation behavior changes abruptly at pH = 7.6-6.6 as a result of protonation of its amino groups.

Journal Article↗

PubMed1979

Partitioning of bile acids into subcellular organelles and the in vivo distribution of bile acids in rat liver.

1. The subcellular distribution of conjugates of cholic acid and chenodeoxycholic acid between cytosol, nuclei, mitochondria and microsomes in rat liver has been determined. 2. The partition coefficients for the distribution of these bile acids between subcellular fractions and buffer have been measured and used to construct a compartmental model of the amounts of conjugated bile acids present in the different subcellular organelles in vivo. 3. This model indicates that a large percentage of the bile acid in the rat liver is found in the nuclear fraction; 42% of the cholic acid conjugates and 27% of the chenodeoxycholic acid conjugates. Substantial amounts of bile acid are also present in microsomes and mitochondria suggesting that published estimates of the amounts of bile acids in these fractions are underestimates. 4. The model also allows the amount of bile acid which is in free solution in cytosol to be determined; 10.9% of the cholic acid conjugates and 4.1% of the chenodeoxycholic acid conjugates in rat liver were present in this fraction. Knowlege of the amount of free bile acid allows possible roles of the cytosolic bile binding proteins to be assessed.

Animals↗