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At least 973 records · Page 54Linked to original sources
PubMed2000

Bile salt toxicity to some bifidobacteria strains: role of conjugated bile salt hydrolase and pH.

The purpose of this work was to study some aspects of bile salt toxicity towards bifidobacteria. A strain (Bifidobacterium coryneforme ATCC 25911) was selected for its lack of conjugated bile salt hydrolase activity (CBSH-), and was used with three deconjugating strains (CBSH+), for study of their growth and viability in the presence of two dihydroxylated conjugated bile salts (tauro- and glyco-deoxycholic acids). The presence of the glycoconjugate induced a more significant growth inhibition for the four strains than the tauroconjugate. The viability of the strains was measured at several pH levels. Glycodeoxycholic acid, but not taurodeoxycholic acid, exerted a lethal effect, which increased at low pH. This phenomenon was more pronounced for the CBSH- strain. We explain some of these results using an hypothesis based on the consequence of dissociation of conjugated and deconjugated bile salts, and the value of their pKa.

Amidohydrolases↗
PubMed1982

Fetal bile salt metabolism: placental transfer of dihydroxy bile salts in sheep.

The bidirectional placental transfer of sodium [11,12-di-3H]chenodeoxycholate and sodium [14C]deoxycholate was studied in conscious pregnant sheep near term. In fetal-to-maternal studies, radiolabeled bile salt was injected into the fetal portal vein, and the daily excretion of radiolabel in maternal hepatic bile was measured over 3-4 days. In maternal-to-fetal studies, the mother received daily injections of radiolabeled bile salt, and the accumulation of label in the fetal pool was measured after 6-9 days. Bile salts were transferred predominantly as the taurine conjugate. Transfer rates were 1) fetus to mother; chenodeoxycholate, 6.7 mumol/24 h and deoxycholate, less than 0.5 mumol/24 h and deoxycholate, 1.4 mumol/24 h. We conclude that, in sheep near term, deoxycholate derived from the mother slowly accumulates in the fetus, while the placenta acts as an excretory route for fetal chenodeoxycholate.

Animals↗
PubMed2005

A nuclear receptor-mediated choleretic action of fibrates is associated with enhanced canalicular membrane fluidity and transporter activity mediating bile acid-independent bile secretion.

Fibrates are commonly used lipid-lowering agents that act via PPARalpha, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARalpha, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2026

Targeting Microbial Bile Salt Hydrolase Reprograms Bile Acid Metabolism and Ameliorates Metabolic Dysfunction-Associated Steatohepatitis in Mice.

Microbial bile salt hydrolase (BSH) plays a central role in shaping bile acid composition and gut-liver metabolic signaling, yet its therapeutic potential in metabolic dysfunction-associated steatohepatitis (MASH) remains incompletely defined. Here, we evaluated the efficacy of the non-absorbable BSH inhibitor GR-7 in a diet induced mouse model of steatohepatitis using early and late intervention strategies with different dosing regimens. GR-7 reduced food intake and exerted stage- and dose-dependent therapeutic effects, with early intervention robustly suppressing hepatic fibrosis even at low dose, whereas late-stage administration of high-dose GR-7 markedly reduced hepatic steatosis and inflammation, as evidenced by decreased liver weight, hepatic triglyceride and cholesterol levels, and plasma ALT. Although late intervention did not result in statistically significant histological reversal of fibrosis, a trend toward improvement was observed, together with suppression of fibrogenic gene expression, suggesting that prolonged treatment may further enhance antifibrotic efficacy. Mechanistically, GR-7 effectively inhibited microbial BSH activity in vivo, leading to reduced cecal unconjugated primary and secondary bile acids-including deoxycholic acid and lithocholic acid, which was associated with improved gut barrier integrity and reduced hepatic inflammation. In parallel, BSH inhibition reprogrammed hepatic bile acid metabolism toward activation of the alternative CYP27A1-mediated synthesis pathway, accompanied by reduced food intake, thereby contributing to improved hepatic lipid accumulation. Furthermore, late-stage high-dose treatment selectively remodeled the hepatic immune landscape rather than fully restoring homeostasis, highlighting immune recalibration as a key component of therapeutic response. Together, these findings identify microbial BSH inhibition as a promising microbiome-targeted therapeutic strategy for MASH.

Gut microbiome↗
PubMed1992

Serum bile acids and the bile acid tolerance test under oral contraception.

Oral contraceptives (OC) have lithogenic properties as shown by a rise in biliary cholesterol secretion and cholesterol saturation index. Since we noted not only a rise in saturation index, but also a reduction in chenodeoxycholate (CDC) pool size and an increase in cholate (C) pool size during oral contraception (30 micrograms ethinylestradiol + 150 micrograms desogestrel), we investigated the endogenous bile acid tolerance test as a potential predictor of this effect on bile acid pool sizes using a cholecystokinin infusion of 55 min duration (1.2 U.kg-1.hr-1) as stimulus of the enterohepatic bile acid circulation in 12 healthy females before and during oral contraception for 3-5 months. Serum C and CDC conjugates were measured at 5-10 min intervals over a period of 150 min and analysed by two specific RIA's. Although no significant correlations between the serum CDC and C measurements and CDC and C pool sizes were found, a significant reduction of nearly 40% for both serum peak levels and the integrated area under the serum curve of CDC conjugates during oral contraception, but not of C conjugates was found. The reduction in serum levels of CDC conjugates during OC using the present model is best explained by both a reduction in CDC pool size and more efficient hepatic uptake of CDC conjugates (consisting of considerably more taurine conjugates during OC use), as well as by an intestinal effect on bile acid absorption under OC.

Adult↗
PubMed1985

[Bile leakage, bile ascites and bilioma--nuclear medicine diagnosis--demonstration of typical cholescintigraphic findings].

Cholescintigraphy (hepatobiliary sequential scintigraphy) with 99m Tc-marked IDA derivatives results in a specific identification of bile in free intraperitoneal fluids (bile ascites) or encapsulated intraperitoneal fluids (bilioma). To detect or exclude a biliary leak, cholescintigraphy was performed in 42 patients. In contrast to sonography and CT ("anatomical imaging"), which are capable of detecting an intraperitoneal accumulation of fluid with high sensitivity, cholescintigraphy ("functional imaging"), alone can help to identify the presence of bile in such fluids, both specifically and on a non-invasive basis. Modern gamma cameras are of such high sensitivity that they can identify even the most minute of activity (bile) quantities with satisfactory anatomic allocation.

Ascites↗
PubMedDate not supplied

Further studies on the properties of bile acids. II. Effect of bile acids on the reactivity of adrenergic and cholinergic receptors in rat intestine.

The effects of bile acids (deoxycholic, cholic and dehydrocholic) were studied on the action of certain autonomic system drugs (isoprenaline, adrenaline, noradrenaline and acetylcholine). It was also tried to explain the causes of these changes in the light of the results of experiments with the widely used antagonists of adrenergic and cholinergic receptors. The experiments were carried out on isolated rat intestine by the method of Magnus. It was found that bile acids decreased the relaxing effect of isoprenaline and caused inversion of the action of adrenaline and noradrenaline on the intestine. Changes in the action of catecholamines are caused by stimulation of alpha-adrenergic receptors enhanced by bile acids, with a simultaneous decreased stimulation of beta-receptors. Bile acids cause also an increase of the effect of acetylcholine on the intestine.

Animals↗
PubMed1994

[Comparison between pharmacologic actions of rabbit bile and bear bile].

In our experiment it was observed that many pharmacologic actions of the rabbit bile were similar to those of bear bile. It was also demonstrated that the effects of the rabbit bile were more obvious than those of bear bile in positive inotropic action, sedation, antitussive action, antihistaminic action and so on.

Animals↗
PubMed1991

New monoclonal antibodies reacting with bile ducts: further insights into the pathogenesis of bile ductular proliferation in biliary diseases.

We have produced a range of monoclonal antibodies which stain human intrahepatic bile ducts of different sizes. Amongst 26 monoclonal antibodies produced, five clones reacted specifically with bile ducts of different sizes, of which three have been maintained in culture and their viability following freezing and thawing confirmed. Staining patterns varied between normal adult liver tissue, normal fetal liver tissue and a variety of hepatobiliary diseases. The antibodies provide further evidence of the immunological heterogeneity of the human intrahepatic biliary tree and support the hypothesis that proliferating bile ductules are derived from periseptal hepatocytes. The preparation of the antibodies, their staining reactions in normal adult, normal fetal and a variety of liver diseases are described.

Adult↗
PubMed1976

The effect of wheat bran upon bile salt metabolism and upon the lipid composition of bile in gallstone patients.

When raw wheat bran was added to the diet of six subjects for 4-6 weeks, chenodeoxycholate (CDC) synthesis increased from 0.46 +/- 0.12 to 0.57 +/- 0.17 mmol/day pool increased from 1.72 +/- 0.47 to 2.19 +/- 0.74 mmol (rho less than 0.05). Deoxycholate (DC) pool size diminished from 1.20 +/- 0.29 to 0.80 +/- 0.16 mmol, but cholate synthesis and pool size were unaffected. Overall, the size of the bile salt pool did not change. In spite of this, when 10 patients with probable cholesterol gallstones took bran supplements for 4-6 weeks, their gallbladder bile aspirated from the duodenum became less saturated with cholesterol. The molar percentage of cholesterol fell from 10.1 +/- 3.1% to 8.6 +/- 2.7% (rho less than 0.01), and the saturation index of bile fell from 1.49 +/- 0.40 to 1.29 +/- 0.38 (rho less than 0.005). Bran probably operates primarily on the colon, reducing the formation or absorption of the bacterial metabolite DC, a substance which impairs CDC synthesis.

Adult↗
PubMed1976

Effect of unsaturated lipids on the bile flow and biliary excretion of cholesterol and bile salts in rats.

When rats were fed safflower oil or coconut oil for 30 days, or soyalecithin (EPL) or egg phospholipids for 7 days, the rates of bile flow, concentration of cholesterol in the bile as well as unsaturation in the biliary phospholipids were markedly higher in the animals receiving the more unsaturated lipids. It is concluded that feeding of lipids containing polyunsaturated fatty acids effects an increase in the unsaturation of the biliary phospholipids and thereby causes increased excretion of cholesterol through the bile.

Animals↗
PubMed1990

Simultaneous determination of conjugated bile acids in human bile.

We describe an optimized liquid chromatographic method for simultaneous analysis of 10 conjugated bile acids in gall bladder and ductal bile. A quick and effective one-step purification with Sep-pak C-18 was adopted. We used a reverse phase C18 stainless steel column and an isocratic mobile phase in a flow programme and monitored the column effluent at 205 nm. The within-day CV ranged from 0.3 to 1.8%, and the between-day CV from 1.2 to 7.2%. Absolute analytical recovery ranged from 89 to 107%. Linearity ranged from 0.3 to 3 mg/mL for most bile acids. The chromatographic analysis was completed in 18 min.

Aged↗
PubMed1985

Studies of bile lipids and bile acids of wild North American black bears in Nova Scotia, showing a high content of ursodeoxycholic acid.

Does ursodeoxycholic acid (UDC) production protect hibernating species of Ursidae against gallstone disease? Five wild bears (Ursis Americana) were studied. Older bears had more UDC than younger ones, suggesting UDC production is an acquired phenomena. Bile salt pools were 10 times larger than that of man and were characteristically conjugated with Taurine alone. The relative composition of the principal lipids in bear bile fell well within the range of cholesterol solubility. Cholesterol gallstones are not reported in Ursidae, probably because of the large bile acid pool and high UDC content.

Animals↗
PubMed1979

Sterol and bile acid metabolism during development. 3. Occurrence of neonatal hypercholesterolemia in guinea pig and its possible relation to bile acid pool.

The relationship of the changes in plasma cholesterol to bile acid pool was studied in the newborn guinea pig. Plasma cholesterol reached the maximum on the fifth day and gradually declined to adult levels. The cholesterol concentration in the high density lipoproteins (HDL) was higher in the newborn guinea pig than in the adult. Plasma triglycerides peaked on the third day and decreased markedly. The bile acid pool increased progressively after birth with a 13-fold increase at 5 days of age. While the hepatic triglycerides decreased sharply in the newborn guinea pig, hepatic cholesterol increased in the first 5 days and then decreased to adult levels. This study has described the occurrence of "neonatal hypercholesterolemia" in the guinea pig and its possible relationship to the low level of bile acid synthesis.

Aging↗
PubMed1988

DNA repair synthesis in primary culture of bovine bile duct epithelial cells induced by chemical agents in relation to bile duct cancer.

Unscheduled DNA synthesis (UDS) was measured autoradiographically in a primary culture of extrahepatic bile duct epithelial cells of Holstein cows following exposure to chemicals known to be capable of developing bile duct cancers in experimental animals, i.e., N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, CAS No. 70-25-7), N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG, CAS No. 4255-77-6), 20-methylcholanthrene (MCA, CAS No. 56-49-5), N-nitrosodimethylamine (DMN, CAS No. 62-75-9) and aflatoxin B1 (AFB1, CAS No. 1162-65-8). MNNG and ENNG induced UDS without addition of S9 mixture. MCA elicited UDS only if S9 mixture was added. Regardless of the presence or absence of S9 mixture, DMN failed to induce UDS. DNA repair by AFB1 was enhanced by the presence of S9 mixture. Therefore, for MNNG, ENNG and high doses of AFB1 activation by the liver is not necessary to exert genotoxic effects and they seem to be capable of direct action on bile duct epithelial cells in the presence of a bilioenteric fistula or anastomosis.

Animals↗
PubMed1993

HPLC-fluorescence determination of bile acids in pharmaceuticals and bile after derivatization with 2-bromoacetyl-6-methoxynaphthalene.

2-Bromoacetyl-6-methoxynaphthalene was used as a pre-chromatographic fluorescent labelling reagent for the high-performance liquid chromatographic (HPLC) analysis of bile acids. The derivatization reaction was performed in an aqueous medium in the presence of tetrahexylammonium bromide by ultrasonication at 40 degrees C to give fluorescent esters which were separated by reversed-phase HPLC and detected fluorimetrically (lambda ex = 300 nm, lambda em = 460 nm). Applications to the determination of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in their pharmaceutical formulations are described. The method was also applied to the determination of free and conjugated bile acids in human bile samples.

Bile↗
PubMed1991

Disposition and metabolism of 2-fluoro-beta-alanine conjugates of bile acids following secretion into bile.

Since 2-fluoro-beta-alanine (FBAL) conjugates of bile acids (BA), the primary biliary metabolites of fluoropyrimidine (FP) drugs, have been suggested to be related to the hepatotoxicity which develops in patients receiving FP chemotherapy by intrahepatic arterial infusion (Proc. Natl. Acad. Sci. USA 84, 5439-5443, 1987), it was important to determine whether they undergo enterohepatic circulation and hence accumulate in the liver and biliary system. In initial studies, sensitivity of FBAL-BA conjugates to hydrolysis by pancreatic enzymes was examined. In subsequent in vivo studies, a model FBAL-BA conjugate, FBAL-chenodeoxycholate (FBAL-CDC), was introduced into the lumen of the small intestine of anesthetized rats with biliary fistulas to quantitate the intestinal absorption, metabolism and tissue distribution of the conjugate. The results indicated that: (1) FBAL-BA conjugates were resistant to hydrolysis by pancreatic enzymes (carboxypeptidase A, carboxypeptidase B and trypsin) and by human pancreatic juice, but were completely hydrolyzed by cholyglycine hydrolase. (2) At least one-half of the administered FBAL-CDC was deconjugated during the process of intestinal absorption, as shown by HPLC analysis of the radioactivity in portal venous blood. (3) Deconjugated FBAL or CDC was reconjugated in liver with other bile acids or amino acids (glycine and taurine), respectively, as shown by radiochromatography of bile. (4) FBAL, formed as a result of hydrolysis of FBAL-CDC, had a wide tissue distribution. In conclusion, FBAL-CDC has a rapid turnover during its enterohepatic circulation due to deconjugation in the intestine and reconjugation in the liver.

Animals↗