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At least 19 recordsLinked to original sources
PubMed1981

The role of taurocholic acid, glycocholic acid and lysolecithin in experimental stress ulcer in the rat.

The stress ulcer formation is enhanced significantly in rats operated with pyloro-jejunostomy and Roux-en-Y anastomosis by taurocholic acid or a mixture of taurocholic and glycocholic acid. However, the incidence of stress ulcers is significantly reduced by adding lysolecithin to the drinking solution containing these bile acids in the same concentration, though lysolecithin alone induces significantly more stress ulcers than tap water in rats with the same operation submitted to immobilisation stress.

Animals↗
PubMed1979

Nuclear and cytosolic distribution of conjugated cholic acid and radiolabelled glycocholic acid in rat liver.

1. Normally fed and cholestyramine-treated rats were injected through the superior mesenteric vein with different amounts of radiolabelled glycoholic acid and the appearance of radioactivity in bile was measured. 2. In normally fed rats radioactivity appeared in bile within 30 s of injection and reached a maximum after 2 1/2 min; in the cholestyramine-treated animals the appearance of radioactivity was slower and less of the injected material was excreted into bile. 3. At 10 min after injection, livers were removed and the amounts of radioactive glycoholic acid and endogenous cholic acid conjugates in nuclei and cytosol were determined; most of the bile acid was found in the cytosol, only small amounts being found in nuclei. 4. Nuclear preparations from both normally fed and cholestyramine-fed rats were extracted with KCl (0.4 M) in an attempt to identify a putative bile acid receptor, but no such receptor was found. 5. Regulation of bile acid synthesis does not involve nuclear binding of bile acids.

Animals↗
PubMed1992

Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit.

Feedback regulation of derepressed hepatic bile acid biosynthesis was studied individually with glycocholic, glycodeoxycholic, and glycoursocholic acids by infusion into bile acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile acid pool (90% glycodeoxycholic acid, 10% glycocholic acid) within 24 hours and elicited maximal bile acid synthesis after about 72 hours, at which time glycocholic acid became the only biliary bile acid (greater than 98%). Replacement of the bile acid pool with glycocholic acid or glycodeoxycholic acid at a rate equivalent to the hepatic endogenous bile acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic acid, the 7 beta-hydroxy epimer of glycocholic acid, failed to suppress synthesis. Hepatic bile acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7 alpha-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic acid. Glycodeoxycholic acid infusion depressed cholesterol 7 alpha-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic acid infusion, were not affected by glycodeoxycholic acid infusion, but increased 19% and 43%, respectively, during glycoursocholic acid infusion. These results show that in rabbits the feedback regulation of hepatic bile acid synthesis depends on the hepatic flux of the normally present endogenous bile acids glycocholic acid and glycodeoxycholic acid but does not respond to the 7 beta-hydroxy glycoursocholic acid. Glycocholic acid inhibits both HMG-CoA reductase and cholesterol 7 alpha-hydroxylase while glycodeoxycholic acid affects primarily cholesterol 7 alpha-hydroxylase. Thus, the regulation of bile acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile acid synthesis.

Animals↗
PubMed1975

[Comparative studies in blood, bile and urine to the biliary excretion and multicompartmental analysis of glycocholic acid in the unanaesthezized pig (author's transl)].

A new model for experimental research in pigs is reported. It allows comparative analyses in blood, bile and urine in the unanaesthetized pig. Preliminary results to the physiology of biliary excretion and multicompartmental analysis of conjugated bile acids emphasize the applicability of the experimental model. On the basis of these results it is pointed out, that it is possible to analize the distribution and excretion kinetics of conjugated bile acids, namely C14-glycocholic acid, by a 3-compartmental analysis.

Administration, Oral↗
PubMed1993

Glycocholic acid in chronic active hepatitis and mild liver diseases.

Serum levels of fasting glycocholic acid were measured in various noncirrhotic liver diseases. Forty-five patients were evaluated, 15 with chronic active hepatitis and 30 with mild liver diseases including chronic persistent hepatitis, steatosis, and minimal changes. There were increased levels of glycocholic acid in 53.3% of chronic active hepatitis cases and in 10% of mile liver disease cases (P = 0.003), and the levels reached by patients with chronic active hepatitis were higher than those in patients with mild liver disease (P < 0.0001). The latter did not show significant differences in their serum levels or in the percentage of abnormal results with respect to control group. There were weak, although significant, correlations between glycocholic acid and transaminases, alkaline phosphatase, gamma-glutamyltranspeptidase, albumin, and gammaglobulin. In the present study, the specificity of glycocholic acid was high in the detection of chronic active hepatitis patients at different cut-off levels. Glycocholic acid appeared to reflect histological severity in this group of noncirrhotic liver diseases and might have practical applications in the management of these patients.

Adolescent↗
PubMed2001

Beneficial effects of glycocholic acid (GCA) on gut mucosal damage in bile duct ligated rats.

In order to investigate the effect of bile acids on gastrointestinal inflammations, bile duct ligated rats (BDL) were treated with GCA (25 mM/ml, oral or colonic) or saline I h before ethanol challenge and twice daily for 3 days in the ileitis group, while GCA was given twice daily for 3 days in the colitis group. BDL reduced the macroscopic and microscopic damage scores in the ileitis group compared to sham operated group, while it had no significant effect on ulcer or colitis groups. However, GCA given in BDL group reduced the ulcer index and microscopic damage in colitis group compared to saline-treated groups, but had no effect in ileitis group. Both BDL and GCA administration in BDL group reduced ileitis- or colitis-induced elevations in MPO levels. GCA administration in BDL group inhibited gastric acid output and volume. Our results suggest that oral or colonic administration of primary bile acids may be useful for the treatment of gastrointestinal inflammations.

Animals↗
PubMed1993

Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests.

Fasting serum levels of glycocholic acid were measured in 142 patients with benign diffuse liver diseases. A total of 63.4% of the whole group of patients, 86.6% of the cirrhotic patients and 31.7% of the noncirrhotic patients had increased serum levels of glycocholic acid. There were significant correlations with blood liver tests associated with liver disease severity such as prothrombin activity and albumin. There were highly significant differences in glycocholic acid levels according to the histological severity of the liver disease, especially when patients with cirrhosis or chronic active hepatitis were compared to the remaining patients and controls. However, discriminant analysis showed that prothrombin activity and albumin were better than glycocholic acid in predicting the histological severity of liver disease. Glycocholic acid serum levels were relatively independent of cholestasis and cytolysis and appeared to be more linked to liver dysfunction. In conclusion, fasting glycocholic acid measurement can be useful in the evaluation and follow-up of liver diseases as a marker of histological severity, and used in addition to other liver tests.

Adolescent↗
PubMed2006

Repeated administration of a vitamin preparation containing glycocholic acid in patients with hepatobiliary disease.

BACKGROUND: Until now, hydrophilic and lipophilic vitamin preparations had to be administered separately during total parenteral nutrition. By addition of glycocholic acid, a vitamin supplement (Cernevit, Baxter, Heidelberg, Germany) was developed that combines all vitamins into one vial. However, little information exists about possible consequences of bile acid administration such as glycocholic acid, especially if liver disease is pre-existing. AIM: To evaluate the effects of total parenteral nutrition with a vitamin preparation containing high doses of glycocholic acid in patients with and without liver disease. METHODS: In a prospective, randomized-controlled trial, 74 patients, 36 of them with hepatobiliary disease, received total parenteral nutrition for 16 +/- 11 days, either with Cernevit or control vitamin supplements. Patients were closely monitored for clinical and biochemical parameters including serum bile acid profiles measured by high-performance liquid chromatography. RESULTS: Serum glycocholic acid increased in patients with liver disease treated with Cernevit, whereas total bile acids did not significantly change. Other liver function tests remained stable during treatment. No adverse events during Cernevit administration were noted except for a reversible slight increase of transaminases in one patient. CONCLUSIONS: Cernevit was well tolerated after repeated dosing, even in patients with severe liver disease. Apart from standard controls of liver biochemistry, no specific surveillance is necessary during treatment with Cernevit.

Adult↗
PubMed1982

Radioimmunoassay of serum glycocholic acid, standard laboratory tests of liver function and liver biopsy findings: comparative study of children with liver disease.

Serum glycocholic acid (SGC) was measured by radioimmunoassay in 277 samples from 122 children with hepatobiliary disorders and from 23 healthy age-matched controls. In patients with hepatobiliary disease the SGC was more frequently abnormal (83%) than values for serum albumin (7%), prothrombin time (17%), bilirubin (22%), alkaline phosphatase (45%), aspartate transaminase (57%) and gammaglutamyl transpeptidase (63%). The cumulative frequency of abnormality of these six tests was equal to that of SGC alone. Serum glycocholic acid concentrations were raised in 13 patients in whom all other tests of liver function were normal. Two of these had clinical and histological evidence of liver disease, while four had biopsy-proven hepatic fibrosis or cirrhosis, and two of three with chronic active hepatitis in remission subsequently relapsed. Four patients have as yet, no other clinical or biochemical evidence of continuing liver disease. Serum glycocholic acid was normal in seven children with abnormal aspartate transaminase or gammaglutamyl transpeptidase in whom there is strong suspicion of significant hepatic disease. A wide range of values of SGC was found with marked overlap between the values found in the different disease entities studied. The SGC value was related to the serum concentration of aspartate transaminase and gammaglutamyl transpeptidase but not to other tests of liver function. Serum glycocholic acid concentration was considered in relation to the severity of histological abnormality in 25 percutaneous liver biopsies. The extent of the rise in SGC was related to the presence or degree of histological severity of oedema in the portal tracts, disruption of the limiting plate, parenchymal fibrosis and hepatocellular necrosis but not to other histological features. The very high incidence of abnormal SGC values found in this study does suggest that in an ordinary inpatient and outpatient service SGC determination is a practical and sensitive indicator of the presence of significant liver disease but for its comprehensive identification aspartate transaminase and gammaglutamyl transpeptidase must also be determined.

Adolescent↗
PubMed1981

Effects of a meal on plasma clearance of [14C]glycocholic acid and indocyanine green in man.

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min--1 m--2, range 376--672 increased to 704, 528--1968; P less than 0.01) and indocyanine green (359, 227--473 increased to 435, 358--985; P less than 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.

Adult↗
PubMed2000

[Synthesis and properties of fluorescent labeled detergents analogues of glycocholic acid].

For studying membrane processes with participation of detergents, fluorescent analogues of glycocholic acid containing p-hydroxybenzyl, 7-nitrobenz-2-oxa-1,3-diazol-4-yl, or fluorescein-5-thiocarbamoyl fluorophore in the glycyl moiety attached to glycocholic acid were synthesized. The fluorophores are in the probes near their carboxyl groups and, in membrane systems, should therefore be situated on the interface and be sensitive to phase transitions. The critical micelle concentrations were determined for the analogues and found to be close to those of cholate and glycocholate in the case of the first two compounds. We presume that the behavior of the probes in membrane systems will mimic the behavior of the bile acid salts.

Detergents↗
PubMed1995

Enhanced secretion of glycocholic acid in a specially adapted cell line is associated with overexpression of apparently novel ATP-binding cassette proteins.

Secretion of anionic endo- and xenobiotics is essential for the survival of animal and plant cells; however, the underlying molecular mechanisms remain uncertain. To better understand one such model system--i.e., secretion of bile acids by the liver--we utilized a strategy analogous to that employed to identify the multidrug resistance (mdr) genes. We synthesized the methyl ester of glycocholic acid (GCE), which readily enters cells, where it is hydrolyzed to yield glycocholic acid, a naturally occurring bile acid. The rat hepatoma-derived HTC cell line gradually acquired resistance to GCE concentrations 20-fold higher than those which inhibited growth of naive cells, yet intracellular accumulation of radiolabel in resistant cells exposed to [14C]GCE averaged approximately 25% of that in nonresistant cells. As compared with nonresistant cells, resistant cells also exhibited (i) cross-resistance to colchicine, a known mdr substrate, but not to other noxious substances transported by hepatocytes; (ii) increased abundance on Northern blot of mRNA species up to 7-10 kb recognized by a probe for highly conserved nucleotide-binding domain (NBD) sequences of ATP-binding cassette (ABC) proteins; (iii) increased abundance, as measured by RNase protection assay, of mRNA fragments homologous to a NBD cRNA probe; and (iv) dramatic overexpression, as measured by Western blotting and immunofluorescence, of a group of 150- to 200-kDa plasma membrane proteins recognized by a monoclonal antibody against a region flanking the highly conserved NBD of mdr/P-glycoproteins. Finally, Xenopus laevis oocytes injected with mRNA from resistant cells and incubated with [14C]GCE secreted radiolabel more rapidly than did control oocytes. Enhanced secretion of glycocholic acid in this cell line is associated with overexpression of ABC/mdr-related proteins, some of which are apparently novel and are likely to include a bile acid transport protein.

ATP-Binding Cassette Transporters↗
PubMed1985

Plasma disappearance of 14C-glycocholic acid as a test of liver dysfunction. Relation to liver histology.

The present study was undertaken to evaluate the clinical usefulness of determining the plasma disappearance of 14C-glycocholic acid in the diagnosis of hepatic disease. This test was compared with the sulfobromophthalein test in 8 control subjects and 46 patients with abnormal liver histology (15 with fatty liver, 20 with alcoholic liver cirrhosis, 6 with primary biliary cirrhosis, and 5 with chronic hepatitis). The best distinction between controls and patients with liver disease was obtained by using the ratio between the plasma radioactivities at 45 and 2 min. However, even then, the 14C-glycocholic acid test had a very low sensitivity for the four groups of patients (0, 60, 50, and 40%, respectively) compared with the sulfobromophthalein test (73%, 90%, 67%, and 100% respectively). The lower sensitivity of the 14C-glycocholic acid test may be explained by the assumption that the clearance of a radioactive tracer dose is more dependent on liver blood flow than on liver function. This test is thus of little clinical value in separating patients with and without normal hepatic histology.

Adult↗
PubMed1978

Kinetics of 14C-glycocholic acid clearance in normal man and in patients with liver disease.

The plasma clearance of a tracer dose of 14C-glycocholic acid, and fasting total serum bile acid concentrations were measured in 14 control subjects and in 38 patients with acute and chronic liver disease. In controls plasma clearance was 415 +/- 24 ml min-1 m-2 (mean +/- SEM), equivalent to a 'first-pass' extraction by the liver of 85%. Clearance was not significantly different from controls in patients with acute hepatitis or active chronic hepatitis, nor in anicteric patients with primary biliary or alcoholic cirrhosis. Thus bile acid clearance was impaired only in icteric chronic liver disease. In contrast, serum bile acid concentrations were abnormal in all but seven patients, six of whom had active chronic hepatitis in complete biochemical remission. The pattern of plasma disappearance of injected 14C-glycocholic acid was biexponential in controls and patients with liver disease, and computer analysis of the curves suggested that there was significant distribution of bile acid outside the vascular space. The preservation of bile acid clearance in anicteric chronic liver disease confirms that it is dependent more on liver blood flow than on liver cell function.

Adult↗
PubMedDate not supplied

[Clinical value of determining serum levels of glycocholic acid in alcoholic lesions of the liver].

To assess the diagnostic value of radioimmunoassay determination of serum levels of glycocholic acid in alcohol-induced chronic diffuse hepatic lesions, this technique was compared by sensitivity and informative content with conventional hepatic tests. Hepatocytic function was measured in combined examination of 83 patients and 30 controls. It is shown that serum glycocholic acid concentration permits detection of early alcohol defects of the liver, excretory dysfunction in particular, control of cholestatic changes, of transformation of hepatic steatosis into hepatitis or cirrhosis, evaluation of cholestasis. The above radioimmunoassay is a useful prognostic tool in decompensated alcohol cirrhosis of the liver.

Adult↗
PubMed1973

Assessment of the 14C-glycocholic acid breath test.

The 1-((14)C)-glycine-glycocholic-acid breath test has been performed on 104 subjects and a normal range established. Abnormal results due to bacterial deconjugation of bile salts were found not only in patients with the "contaminated bowel" syndrome and in those with ileal resection but also in a third group, patients with cholangitis. Abnormal results were also found in patients with gastrocolic fistula and staphylococcal enterocolitis, while mildly abnormal results were also found in some patients with liver disease.

Bacteria↗