deoxycholic-acid and Cholestasis

Topics: Bile; Biliary Tract Neoplasms; Cholestasis; Deoxycholic Acid; Drainage; Enteral Nutrition; Humans; Immunoglobulin A, Secretory; Nutrition Assessment; Parenteral Nutrition; Postoperative Care; Risk

Topics: Bile Acids and Salts; Biliary Tract Diseases; Celiac Disease; Chenodeoxycholic Acid; Cholelithiasis; Cholestasis; Cholic Acids; Colonic Neoplasms; Deoxycholic Acid; Diarrhea; Humans; Intestinal Diseases; Intestine, Small; Lipid Metabolism; Lithocholic Acid; Liver; Liver Circulation; Malabsorption Syndromes; Portal System

Topics: Bile Acids and Salts; Bile Ducts; Cholestasis; Cholestyramine Resin; Deoxycholic Acid; Disease Models, Animal; Female; Glucuronates; Hepatitis; Humans; Ligation; Lithocholic Acid; Liver; Liver Cirrhosis; Male; Phenobarbital; Pregnancy; Pregnancy Complications; Sterols; Sulfates

Topics: Bile; Bile Acids and Salts; Biological Transport, Active; Chenodeoxycholic Acid; Child; Child, Preschool; Cholestasis; Cholesterol; Cholic Acids; Deoxycholic Acid; Humans; Infant; Infant Nutrition Disorders; Infant, Newborn; Lithocholic Acid; Liver; Liver Diseases; Malabsorption Syndromes; Surface Properties

Topics: Animals; Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Humans; Lithocholic Acid; Liver; Rats; Sulfates

The role of preoperative lactulose and bile salts in the prevention of postoperative renal failure in patients with obstructive jaundice has been evaluated in a prospective randomized trial. One hundred and two patients undergoing surgery for obstructive jaundice (bilirubin greater than 100 mumols/l) were randomized into three groups: those receiving preoperative oral lactulose (n = 35), those receiving oral sodium deoxycholate (n = 32) and a control group of patients receiving no specific treatment (n = 35). All patients received intravenous fluids commencing the night before surgery. One patient in the control group and none in the treatment groups developed postoperative renal failure. Postoperative deterioration of renal function in patients with normal preoperative function was significantly more common in the control group than in the treatment groups (chi 2 = 8.1, d.f. = 2, P less than 0.02). The incidence of renal failure and impairment was lower in this control group than that reported in previous studies. This may be due to the introduction of adequate preoperative hydration. Additional protection occurs by the preoperative administration of either lactulose or sodium deoxycholate.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Cholestasis; Deoxycholic Acid; Female; Humans; Kidney; Lactulose; Male; Middle Aged; Postoperative Complications; Preoperative Care; Prospective Studies

Surgical treatment for the relief of obstructive jaundice is still complicated by postoperative acute renal failure in almost 10 per cent of patients. Renal failure in the patient with jaundice is associated with the presence of bacterial endotoxin in the peripheral blood, and enteric endotoxin absorption is facilitated by the absence of bile salts from the intestine. Oral replacement of bile salts should prevent endotoxemia and renal failure. Forty-six patients with jaundice were studied. Twelve patients received sodium deoxycholate preoperatively, 12 received chenodeoxycholic acid and 22 acted as controls. Endotoxemia was measured by the limulus test and renal function assessed by 24 hour creatinine clearance. No patient given deoxycholate preoperatively had systemic endotoxemia or postoperative impairment of renal function. Endotoxemia was reduced in the chenodeoxycholic acid group, but not significantly, and renal function was not protected. Sodium deoxycholate is undergoing further evaluation in a multicenter randomized prospective study.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Creatine; Deoxycholic Acid; Drug Evaluation; Endotoxins; Humans; Intraoperative Care; Kidney; Mannitol; Postoperative Complications; Premedication

Forty patients with obstructive jaundice (bilirubin greater than 100 mumol/l) were entered into a randomized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy. Pre-operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients (P less than 0.001). Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients (P less than 0.05). There was no significant difference in systemic venous endotoxaemia, renal function or postoperative morbidity or mortality. This study suggests pre-operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice.

Topics: Administration, Oral; Adolescent; Adult; Aged; Cholestasis; Clinical Trials as Topic; Creatinine; Deoxycholic Acid; Endotoxins; Female; Humans; Intraoperative Complications; Male; Middle Aged; Premedication; Random Allocation; Toxemia; Ursodeoxycholic Acid

Drug-induced intrahepatic cholestasis is characterized by cellular accumulation of bile acids (BAs), whose mechanisms remain poorly understood. The present study aimed to analyze early and progressive alterations of BA profiles induced by cyclosporine A, chlorpromazine, troglitazone, tolcapone, trovafloxacin, and tacrolimus after 4-hour, 24-hour, and 6-day treatments of differentiated HepaRG cells. In BA-free medium, the potent cholestatic drugs cyclosporine A, chlorpromazine, and troglitazone reduced endogenous BA synthesis after 24 hours, whereas the rarely cholestatic drugs tolcapone, trovafloxacin, and tacrolimus reduced BA synthesis only after 6 days. In the presence of physiologic serum BA concentrations, cyclosporine A, chlorpromazine, and troglitazone induced early and preferential cellular accumulation of unconjugated lithocholic, deoxycholic, and chenodeoxycholic acids that increased 8- to 12-fold and 47- to 50-fold after 24 hours and 6 days, respectively. Accumulation of these hydrophobic BAs resulted from strong inhibition of amidation, and in addition, for lithocholic acid reduction of its sulfoconjugation, and was associated with variable alterations of uptake and efflux transporters. Trovafloxacin also caused BA accumulation, especially after 6 days, whereas tolcapone and tacrolimus were still without effect. However, when exogenous BAs were added to the medium at cholestatic serum concentrations, a 6-day treatment with all drugs resulted in cellular BA accumulation with higher folds of chenodeoxycholic and lithocholic acids. At the tested concentration, tolcapone had the lowest effect. These results bring the first demonstration that major cholestatic drugs can cause preferential and progressive in vitro cellular accumulation of unconjugated toxic hydrophobic BAs and bring new insights into mechanisms involved in drug-induced cellular accumulation of toxic BAs.

Topics: Amides; Bile Acids and Salts; Cell Line; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Humans; Lithocholic Acid; Liver; Organic Anion Transporters, Sodium-Dependent; Sulfates; Symporters; Taurocholic Acid

Clinicians sometimes encounter difficulty in choosing a therapeutic strategy due to the uncertainty regarding the type of liver injury. In particular, cholestasis is difficult to diagnose by conventional markers at an early stage of disease. The aim of this study was to identify promising biomarkers for distinguishing the symptom-based types of liver injury (e.g. hepatocellular injury, cholestasis), which was derived from a rigorously statistical perspective. The associations between diagnostic biomarkers (e.g. bile acid components, oxidative stress markers and liver fibrosis markers) and the liver injury types were assessed by a multiple logistic regression analysis using 304 blood samples from patients with liver disease. As a result, reductions in the lithocholic acid (LCA) and deoxycholic acid (DCA) levels, and elevation of the serum sulfated bile acid (SSBA), liver fibrosis marker IV collagen (type IV collagen), hyaluronic acid (HA) and reactive oxygen species (ROS) levels were all significantly associated with cholestasis. On the other hand, elevations in the LCA and type IV collagen levels, and a reduction in the ursodeoxy cholic acid (UDCA) level, were significantly associated with hepatocellular injury. The receiver operating characteristic (ROC) analyses showed that the largest area under the ROC curve (AUC) was found for ROS, followed by DCA, HA, LCA, SSBA and type IV collagen in the cholestatic-type cases. These results indicated that ROS, the secondary bile acid levels such as DCA and LCA, and SSBA are promising biomarkers for cholestasis and for classifying the type of liver injuries. This comprehensive approach will allow for an accurate diagnosis, which will facilitate the selection of an appropriate therapy at the onset of disease.

Topics: Aged; Bile Acids and Salts; Biomarkers; Cholestasis; Collagen Type IV; Deoxycholic Acid; Female; Humans; Hyaluronic Acid; Lithocholic Acid; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Sulfates

The accumulation of bile acids affects mitochondria causing oxidative stress. Antioxidant defense is accepted to include biotransformation of biliverdin (BV) into bilirubin (BR) through BV reductase α (BVRα). The mutation (c.214C>A) in BLVRA results in a non-functional enzyme (mutBVRα). Consequently, homozygous carriers suffering from cholestasis develop green jaundice. Whether BVRα deficiency reduces BV-dependent protection against bile acids is a relevant question because a screening of the mut-BLVRA allele (a) in 311 individuals in Greenland revealed that this SNP was relatively frequent in the Inuit population studied (1% a/a and 4.5% A/a). In three human liver cell lines an inverse correlation between BVRα expression (HepG2>Alexander>HuH-7) and basal reactive oxygen species (ROS) levels was found, however the ability of BV to reduce oxidative stress and cell death induced by deoxycholic acid (DCA) or potassium dichromate (PDC) was similar in these cells. The transduction of BVRα or mutBVRα in human placenta JAr cells with negligible BVRα expression or the silencing of endogenous BVRα expression in liver cells had no effect on DCA-induced oxidative stress and cell death or BV-mediated cytoprotection. DCA stimulated both superoxide anion and hydrogen peroxide production, whereas BV only inhibited the latter. DCA and other dihydroxy-bile acids, but not PDC, induced up-regulation of both BVRα and heme oxygenase-1 (HO-1) in liver cells through a FXR independent and BV insensitive mechanism. In conclusion, BV exerts direct and BVRα-independent antioxidant and cytoprotective effects, whereas bile acid accumulation in cholestasis stimulates the expression of enzymes favoring the heme biotransformation into BV and BR.

Topics: Animals; Biliverdine; Cholestasis; Deoxycholic Acid; Free Radical Scavengers; Gene Expression; HEK293 Cells; Heme Oxygenase-1; Hep G2 Cells; Humans; Liver; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Oxidoreductases Acting on CH-CH Group Donors; Potassium Dichromate; Protective Factors; Reactive Oxygen Species

The blood brain barrier tightly regulates the passage of molecules into the brain and becomes leaky following obstructive cholestasis. The aim of this study was to determine if increased serum bile acids observed during cholestasis permeabilize the blood brain barrier.. Rats underwent bile duct ligation or deoxycholic or chenodeoxycholic acid injections and blood brain barrier permeability assessed. In vitro, the permeability of rat brain microvessel endothelial cell monolayers, the expression and phosphorylation of occludin, ZO-1 and ZO-2 as well as the activity of Rac1 was assessed after treatment with plasma from cholestatic rats, or bile acid treatment, in the presence of a Rac1 inhibitor.. Blood brain barrier permeability was increased in vivo and in vitro following bile duct ligation or treatment with bile acids. Associated with the bile acid-stimulated increase in endothelial cell monolayer permeability was elevated Rac1 activity and increased phosphorylation of occludin. Pretreatment of endothelial cell monolayers with a Rac1 inhibitor prevented the effects of bile acid treatment on occludin phosphorylation and monolayer permeability.. These data suggest that increased circulating serum bile acids may contribute to the increased permeability of the blood brain barrier seen during obstructive cholestasis via disruption of tight junctions.

Topics: Aminoquinolines; Animals; Bile Ducts; Blood-Brain Barrier; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Disease Models, Animal; Endothelial Cells; Ligation; Male; Microvessels; Occludin; Permeability; Phosphorylation; Pyrimidines; rac1 GTP-Binding Protein; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tight Junctions; Tissue Culture Techniques; Zonula Occludens-1 Protein; Zonula Occludens-2 Protein

Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G), glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.

Topics: Apoptosis; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Female; Hep G2 Cells; Humans; Lithocholic Acid; Liver; Male

To investigate the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation (BDL).. Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley (SD) rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid (DCA) in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase (LDH) activity was determined in the supernatant of cultivated hepatocytes.. Serum alanine transaminase levels increased to about 600 U/L 1 d after BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.. These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Calcium; Cells, Cultured; Chlorides; Cholagogues and Choleretics; Cholestasis; Deoxycholic Acid; Diet; Disease Models, Animal; Glycine; Glycine Agents; Hepatocytes; Kupffer Cells; L-Lactate Dehydrogenase; Ligation; Liver Diseases; Male; Rats; Rats, Sprague-Dawley

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), the 7alpha-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17alpha-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 micromol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO(3)(-)), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO(3)(-) output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na(+) taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease.

Topics: Animals; Bile; Bile Ducts; Cholanes; Cholestasis; Cholesterol 7-alpha-Hydroxylase; Chromatography, High Pressure Liquid; Deoxycholic Acid; Dose-Response Relationship, Drug; Ethinyl Estradiol; Gas Chromatography-Mass Spectrometry; Male; Micelles; Molecular Structure; Phospholipids; Rats; Rats, Sprague-Dawley; RNA, Messenger; Steroid 12-alpha-Hydroxylase; Steroids, Fluorinated; Ursodeoxycholic Acid

In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against experimentally induced gastrointestinal, pancreatic, and hepatic damage. This study was undertaken to examine if eupatilin modulates bile acid-induced hepatocyte apoptosis.. Huh-BAT cells, a human hepatocellular carcinoma cell line stably transfected with a bile acid transporter, were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. Eupatilin's in vivo effect on bile acid-induced hepatocyte apoptosis was explored in bile duct-ligated rats.. Eupatilin significantly reduced bile acid-mediated hepatocyte apoptosis by attenuating bile acid-induced caspase 8 cleavage. Eupatilin diminished the bile acid-induced activation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In particular, the eupatilin-mediated inhibition of bile acid-induced c-Jun N-terminal kinase activation was found to be responsible for attenuating caspase 8 cleavage. Moreover, eupatilin diminished hepatocyte apoptosis in bile duct-ligated rats.. Eupatilin attenuates bile acid-induced hepatocyte apoptosis by suppressing bile acid-induced kinase activation. Therefore, eupatilin might be therapeutically efficacious in a variety of human liver diseases associated with cholestasis.

Topics: Animals; Apoptosis; Caspase 8; Cell Line, Tumor; Cholestasis; Deoxycholic Acid; Flavonoids; Hepatocytes; Humans; Immunoblotting; In Situ Nick-End Labeling; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Microscopy, Fluorescence; Models, Animal; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley

Inappropriate activation of the mineralocorticoid receptor (MR) results in renal sodium retention and potassium loss in patients with liver cirrhosis. Recent evidence suggested that this MR activation is, at least in part, a result of bile acid-dependent reduction in 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) activity, an enzyme preventing cortisol-dependent activation of MR by converting cortisol to cortisone. Here, we investigated the molecular mechanisms underlying bile acid-mediated MR activation. Analysis of urinary bile acids from 12 patients with biliary obstruction revealed highly elevated concentrations of chenodeoxycholic acid (CDCA), cholic acid (CA), and deoxycholic acid (DCA), with average concentrations of 50-80 microm. Although CDCA and DCA both mediated nuclear translocation of MR in the absence of 11 beta HSD2 and steroids in transiently expressing HEK-293 cells, the transcriptional activity of MR was not stimulated. In contrast, CDCA and DCA both inhibited 11 beta HSD2 with IC(50) values of 22 and 38 microm, respectively and caused cortisol-dependent nuclear translocation and increased transcriptional activity of MR. LCA, the bile acid that most efficiently inhibited 11 beta HSD2, was present at very low concentrations in cholestatic patients, whereas the weak inhibitor CA did not cause MR activation. In conclusion, these findings indicate that CDCA, and to a lesser extent DCA, by inhibiting 11 beta HSD2, mediate cortisol-dependent nuclear translocation and transcriptional activation of MR and are responsible at least for a part of the sodium retention and potassium excretion observed in patients with biliary obstruction.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Active Transport, Cell Nucleus; Animals; Bile Acids and Salts; Cells, Cultured; Chenodeoxycholic Acid; CHO Cells; Cholestasis; Cricetinae; Deoxycholic Acid; Female; Fluorescent Antibody Technique; Gallstones; Gas Chromatography-Mass Spectrometry; Humans; Hydrocortisone; Hydroxysteroid Dehydrogenases; Kinetics; Male; Models, Chemical; Receptors, Mineralocorticoid; Transcriptional Activation

Topics: Animals; Cholagogues and Choleretics; Cholestasis; Deoxycholic Acid; Glucuronates; Glutathione; Male; Microsomes, Liver; Nikethamide; Rats; S-Adenosylmethionine; Ursodeoxycholic Acid; Vitamin E; Xenobiotics

Hydrophobic bile acids, such as deoxycholic acid produce cholestatic liver injury. Ursodeoxycholic acid has been shown to be useful in the treatment of cholestatic liver disease.. In this study, we investigated the effects of deoxycholic acid or ursodeoxycholic acid (1% of diet, for 14 days) and their combination (1% each) on expression of hepatic cytochrome P450 isozymes, their related enzyme activities and mRNA level in rats.. Adding 1% deoxycholic acid to chow caused a marked increase in serum total bilirubin (47-fold) and total bile acid (8-fold) concentrations and in alkaline phosphatase (2.5-fold, p<0.01) and alanine aminotransferase activities (23.5-fold, p<0.01). Adding the same dose of ursodeoxycholic acid along with the deoxycholic acid mitigated both the rise in serum total bilirubin and bile acid concentrations and that in alkaline phosphatase and alanine aminotransferase activities, although the use of ursodeoxycholic acid alone did not affect any of the above. Feeding 1% deoxycholic acid caused a decrease (48% of control) in total cytochrome P450 content in hepatic microsomes. Addition of 1% ursodeoxycholic acid along with the 1% deoxycholic acid completely prevented the decrease in total cytochrome P450 content. Feeding ursodeoxycholic acid alone did not affect the total cytochrome P450 content. The expression of cytochrome P450 2B1, 2E1, 3A2, 2C6, 2C11 and 4A1 proteins in hepatic microsomes was decreased by deoxycholic acid (44, 51, 23, 59, 30 and 74% of control, respectively). Likewise, the activities of cytochrome P450 2B1 (pentoxyresorufin O-depentylation), 2E1 (aniline p-hydroxylation) and 3A2 (testosterone 6beta-hydroxylation) isozymes and the 3A2 mRNA levels in liver were decreased by deoxycholic acid. Addition of 1% ursodeoxycholic acid to 1% deoxycholic acid also prevented the decrease in these cytochrome P450 proteins, related enzyme activities and mRNA levels in liver.. These results indicate that, in rats with deoxycholic acid-induced liver injury, ursodeoxycholic acid prevents the decrease in hepatic cytochrome P450 isozymes and suggest that ursodeoxycholic acid is useful for the treatment of liver injury in terms of aiding the normalization of the hepatic drug-metabolizing system.

Topics: Animals; Cholagogues and Choleretics; Cholestasis; Cytochrome P-450 Enzyme System; Deoxycholic Acid; Liver; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Ursodeoxycholic Acid

Topics: Cholagogues and Choleretics; Cholestasis; Deoxycholic Acid; Gas Chromatography-Mass Spectrometry; Humans; Ursodeoxycholic Acid

The aim of this study was to define whether N-acetylglucosaminidation is a selective conjugation pathway of structurally related bile acids in humans. The following bile acids released enzymatically from N-acetylglucosaminides were identified: 3 alpha,7 beta-dihydroxy-5 beta-cholanoic (ursodeoxycholic), 3 beta, 7 beta-dihydroxy-5 beta-cholanoic (isoursodeoxycholic), 3 beta,7 beta-dihydroxy-5 alpha-cholanoic (alloisoursodeoxycholic), 3 beta,7 beta-dihydroxy-5-cholenoic, 3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholanoic, and 3 alpha,6 alpha,7 beta-trihydroxy-5 beta-cholanoic acids. The selectivity of conjugation was studied by administration of 0.5 g ursodeoxycholic (UDCA) or hyodeoxycholic (HDCA) acids, labeled with 13C, to patients with extrahepatic cholestasis, and of 0.5 g of 13C-labeled chenodeoxycholic acid (CDCA) to patients with extra- or intrahepatic cholestasis. After administration of [24-13C]-CDCA, labeled glucosides, and the glucuronide of CDCA were excreted in similar amounts. Labeled N-acetylglucosaminides of UDCA and isoUDCA were also formed. When [24-13C]-UDCA was given, 13C-label was detected in the N-acetylglucosaminide, the glucosides, and the glucuronide of UDCA, and in the N-acetylglucosaminide of isoUDCA. In the patient studied, 32% of the total UDCA excreted in urine was conjugated with N-acetylglucosamine. In contrast, 96% of the excreted amount of [24-13C]HDCA was glucuronidated, and 13C-labeled glucosides but no N-acetylglucosaminide were detected. The selectivity of N-acetylglucosaminidation towards bile acids containing a 7 beta-hydroxyl group was confirmed in vitro using human liver and kidney microsomes and uridine diphosphate glucose (UDP)-N-acetylglucosamine. These studies show that N-acetylglucosaminidation is a selective conjugation pathway for 7 beta-hydroxylated bile acids.

Topics: Acetylglucosamine; Administration, Oral; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Glycosides; Humans; Hydroxylation; Liver Diseases; Mass Spectrometry; Ursodeoxycholic Acid

In order to study the glycosidic conjugation of chenodeoxycholic, hyodeoxycholic, and ursodeoxycholic acids in patients with cholestasis after oral administration of pharmacological amounts of the respective bile acids avoiding the application of radioactive tracers we synthesized [24-13C]chenodeoxycholic, [24-13C]hyodeoxycholic, and [24-13C]ursodeoxycholic acids. The reaction intermediates of the bile acid syntheses were characterized by infrared spectroscopy. Purity was confirmed using thin-layer chromatography as well as gas chromatography-mass spectrometry. The 13C atom excess of approximately 90% of the synthesized bile acids was the same as the 13C atom excess of the sodium [13C]cyanide used for the labeling reaction confirming the successful synthesis. After oral administration of 0.5 g of [24-13C]ursodeoxycholic acid to a healthy volunteer, 13C label was detected in the nonamidated and glycine- or taurine conjugated glucosides and the N-acetylglucosaminide of ursodeoxycholic acid in urine. This establishes ursodeoxycholic acid as the first bile acid so far known to undergo both of the recently described glycosidic conjugation reactions in humans.

Topics: Administration, Oral; Carbon Isotopes; Chenodeoxycholic Acid; Cholestasis; Chromatography, Thin Layer; Deoxycholic Acid; Gas Chromatography-Mass Spectrometry; Humans; Isotope Labeling; Spectrophotometry, Infrared; Ursodeoxycholic Acid

The role of hepatocytes in bile acid and cholesterol metabolism has been extensively studied. By contrast, nothing is known about the role of bile ductular epithelial cells in cholesterol and bile acid metabolism. The purpose of the current studies was to establish whether bile ductular epithelial cells synthesize cholesterol, bile acids or both and to determine whether these cells are capable of metabolizing (hydroxylating, conjugating) bile acids. Bile ductular epithelial cells were isolated from rat liver after ligation of the common bile duct for 6 to 8 wk. Bile ductular epithelial cells were essentially free (greater than 99%) of hepatocytes and were histochemically positive (greater than 80%) for gamma-glutamyl transpeptidase activity. Cholestatic hepatocytes were simultaneously isolated and characterized with regard to their ability to synthesize and metabolize bile acids. Incubation of bile ductular epithelial cells with [14C]-acetate resulted in rapid labeling of cellular cholesterol, suggesting that these cells have a complete cholesterol biosynthetic pathway. The addition of [4-14C]-cholesterol to bile ductular epithelial cells did not lead to detectable synthesis of [14C]-bile acids. [24-14C]-Cholic acid, [24-14C]-deoxycholic acid, [24-14C]-lithocholic acid and [3H]-ursodeoxycholic acid were individually added to bile ductular epithelial cells and incubated for 24 or 48 hr. Bile acid metabolites were extracted and separated by C-18 reverse-phase high-performance liquid chromatography or thin-layer chromatography. Bile ductular epithelial cells conjugated deoxycholic acid, ursodeoxycholic acid and lithocholic acid to glycine and taurine. Surprisingly, no conjugation of cholic acid was detected. Conjugated lithocholic acid was further metabolized to highly polar metabolite(s), possibly beta-muricholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bile Acids and Salts; Bile Ducts; Cell Separation; Cells, Cultured; Cholestasis; Cholesterol; Cholic Acid; Cholic Acids; Deoxycholic Acid; Epithelial Cells; Epithelium; Lithocholic Acid; Male; Rats; Rats, Inbred Strains; Ursodeoxycholic Acid

The prevalence of biliary and hepatic diseases is increasing in patients with cystic fibrosis as more of them reach adult life. There is no effective treatment or method of preventing cholestasis in cystic fibrosis, although beneficial effects have been ascribed to the tertiary bile acid, ursodeoxycholate, in other forms of chronic cholestasis. We evaluated prospectively the effects of a six month course of ursodeoxycholate (15-20 mg/kg per day) in eight, mostly adult, patients with cystic fibrosis and chronic cholestasis. Bile acid treatment improved inflammatory activity (average decrease in alanine aminotransferase, 60%, p less than 0.005) and cholestasis (alkaline phosphatase, 47%; p less than 0.01) in all patients. Quantitative liver function, measured by 45 minute sulphobromophthalein retention and by the 14C-aminopyrine breath test, improved in all patients while galactose elimination capacity showed a slight decrease. Patients' nutritional state improved as evidenced by a 1.8 kg weight gain and an increase in muscle mass suggested by a 26% increase in 24 hour urinary creatinine excretion. Steatorrhea was not affected by bile acid treatment. Ursodeoxycholic acid may be beneficial in the treatment of chronic cholestasis in cystic fibrosis by improving liver function and also the patient's nutritional state.

Topics: Adolescent; Adult; Child; Cholestasis; Chronic Disease; Cystic Fibrosis; Deoxycholic Acid; Female; Humans; Liver; Liver Function Tests; Male; Nutritional Status; Prospective Studies; Ursodeoxycholic Acid

Systemic endotoxaemia is associated with postoperative renal dysfunction in obstructive jaundice, and can be prevented by the pre-operative administration of certain bile salts. In order to find the most effective bile salt for use in this condition, a comparison of the anti-endotoxic activities of different bile salts was performed. Bile salts were incubated in vitro with endotoxin and the resultant endotoxin level was measured with a quantitative limulus assay. The in vivo effects of different oral bile salts on the intestinal absorption of radiolabelled endotoxin from rats with obstructive jaundice were compared. The in vitro and in vivo anti-endotoxic activities of bile salts related to their known detergent activities. Deoxycholic acid and its conjugates were the most effective and should be the bile salts of choice for further clinical evaluation in obstructive jaundice in man.

Topics: Animals; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acid; Cholic Acids; Deoxycholic Acid; Endotoxins; Escherichia coli; Glycodeoxycholic Acid; Intestinal Absorption; Male; Rats; Rats, Inbred Strains; Taurocholic Acid; Taurodeoxycholic Acid; Ursodeoxycholic Acid

The effects of ursodeoxycholate administration on the biliary excretion of the antibiotics cefotiam and sulbenicillin were studied in five patients with stable hepatic function receiving percutaneous transhepatic biliary drainage for obstructive jaundice. Cefotiam (I g) and sulbenicillin (2 g) were administered intravenously before and after ursodeoxycholate administration, and the maximum concentrations of the antibiotics in the bile and total amounts excreted in the bile during the 4 h after administration were determined. After ursodeoxycholate administration, both the maximum concentration of cefotiam in the bile and the amount excreted increased significantly. Ursodeoxycholate also increased the peak concentration and total excretion of sulbenicillin. For both cefotiam and sulbenicillin, the amount of antibiotic excreted in the bile during the 4 h after administration showed a significant correlation with the amount of bile acids excreted in the bile. This strongly suggests a common mechanism for the biliary excretion of these antibiotics and bile acids. Ursodeoxycholate administration is a benign way to increase both the concentration and the total amount of antibiotic excreted in the bile. Therefore, it may be useful in the treatment of serious biliary tract infections, especially in patients receiving biliary drainage.

Topics: Aged; Bile; Bile Acids and Salts; Cefotaxime; Cefotiam; Cholestasis; Deoxycholic Acid; Drainage; Female; Humans; Male; Middle Aged; Penicillin G; Sulbenicillin; Ursodeoxycholic Acid

Topics: Cholestasis; Deoxycholic Acid; Double-Blind Method; Follow-Up Studies; Humans; Liver Cirrhosis, Biliary; Prospective Studies; Ursodeoxycholic Acid

Topics: Aged; Bile; Cefotaxime; Cefotiam; Cholestasis; Deoxycholic Acid; Drainage; Female; Humans; Male; Middle Aged; Ursodeoxycholic Acid

Preoperative administration of the simple bile salt sodium deoxycholate has been shown in this study to prevent postoperative endotoxaemia and renal failure in patients with obstructive jaundice. Fifty-four per cent of jaundiced patients not given the salt were found to have systemic endotoxaemia, associated with renal impairment in two-thirds of the cases. No patient given sodium deoxycholate 500 mg 8 hourly for 48 hours before operation had portal or systemic endotoxaemia, and none had evidence of renal impairment (P less than 0 X 02, X2 with Yates' correction). The incidence of endotoxaemia in untreated jaundiced patients was very significantly greater than in non-jaundiced patients undergoing elective upper abdominal surgery (P less than 0 X 005), but this difference is abolished by the prophylactic administration of the oral bile salt. The mechanism of action of bile salts in preventing endotoxin absorption from the small bowel has been investigated, and the lack of any significant alteration in the small bowel microbial flora in obstructive jaundice suggests that a direct effect on the endotoxin molecule is involved. Nearly 20 per cent of patients with obstructive jaundice still develop postoperative renal insufficiency, but preoperative prophylactic use of sodium deoxycholate should reduce this very significantly.

Topics: Acute Kidney Injury; Aged; Bacteria; Bile Acids and Salts; Cholestasis; Creatinine; Deoxycholic Acid; Endotoxins; Female; Humans; Intestinal Secretions; Intestines; Male; Middle Aged; Postoperative Complications; Premedication

Jaundiced serum from common bile duct ligated rats, added to cultured heart cells, decreased the beating rate, caused an early cessation of beating and production of higher levels of lactate in the media. Deoxycholate and cholate are the main bile acids in jaundiced serum; deoxycholate caused similar effects, which suggests that it is the toxic substance responsible for heart function alterations seen in patients with severe jaundice.

Topics: Animals; Bile Acids and Salts; Cells, Cultured; Cholestasis; Cholic Acids; Common Bile Duct; Deoxycholic Acid; Heart Rate; Ligation; Myocardial Contraction; Rats; Rats, Inbred Strains

A combined infusion of taurocholate (TC) and glycoursodeoxycholate (GU) resulted in a longer choleretic period and a significantly higher excretion of TC compared with the infusion of TC alone, as has been previously observed for the combined infusion of tauroursodeoxycholate (TU) and TC in the rat. It was concluded that GU is as effective as TU in preventing TC induced cholestasis in this species.

Topics: Animals; Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Drug Evaluation, Preclinical; Rats; Secretory Rate; Taurochenodeoxycholic Acid; Taurocholic Acid; Ursodeoxycholic Acid

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.

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Diagnosis, Differential; Humans; Liver Cirrhosis, Biliary; Liver Diseases; Spectrometry, Fluorescence

The pregnancies of two patients with mild intrahepatic cholestasis of pregnancy (RCP) were followed with detailed analyses of bile acids in urine. About twenty-five different bile acids were determined by GC/MS following separation according to mode of conjugation. The results were collated with the clinical course of the disease. The first detectable change in bile acid excretion was the appearance of tetrahydroxylated bile acids at about the 30th gestational week. Somewhat later and concomitant with the rise in urinary oestriol, the total bile acid excretion started to increase. In one of the patients, who had a maximum total excretion of 84 mumol/24 h, deoxycholic acid was a major constituent, comprising about 40% of the total. The same patient had only slightly elevated levels of tetrahydroxylated bile acids and serum amino-transferases. The possible effect of low-fat diet on these results is discussed. Monohydroxylated bile acids were present throughout the pregnancies in small amounts and their role as aetiological factors is discussed. The care of RCP patients is outlined, and the need for simple, specific and quantitative methods for following the course of RCP is pointed out.

Topics: Adult; Bile Acids and Salts; Cholestasis; Deoxycholic Acid; Dietary Fats; Estriol; Female; Humans; Pregnancy; Pregnancy Complications; Pruritus; Recurrence; Transaminases

Bile acid compositions in the serum, urine, bile, and feces were examined in a typical case of benign recurrent intrahepatic cholestasis for a period of 3 yr. The serum cholesterol level remained almost constant. The serum and urinary levels of total bile acids increased markedly during the icteric phase but returned to normal toward the anicteric phase. Daily fecal excretion of bile acids in the anicteric phase was about three times the normal value. Bile acids in the bile and feces, and in the serum and urine, mainly consisted of chenodeoxycholic and cholic acids, with little deoxycholic acid even in the anicteric phase. Scarcely any coprostanol was found in the feces. These observations suggest that metabolism by intestinal bacteria was altered in this patient. The ratio of cholic acid/chenodeoxycholic acid in the serum was above 2.0 in the icteric phase but was reduced to 0.9 in the anicteric phase. At least three unusual bile acids, designated as peak 7a, 11, and 13, were detected in the feces. The amount of bile acid in peak 7a reached about 10% of the total in the anicteric phase.

Topics: Adult; Bile; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Feces; Humans; Lithocholic Acid; Male; Recurrence

Topics: Animals; Cholestasis; Deoxycholic Acid; Enzyme Induction; In Vitro Techniques; Kinetics; Lipid Metabolism; Male; Methylcholanthrene; Microsomes, Liver; Mixed Function Oxygenases; Models, Biological; Oxidoreductases; Oxygen Consumption; Peroxides; Phenobarbital; Rats

Topics: Bile Acids and Salts; Cholecystectomy; Cholelithiasis; Cholestasis; Common Bile Duct; Deoxycholic Acid; Gallstones; Humans; Lithocholic Acid

We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). Before radioimmunoassay, 0.1-mL serum samples were precipitated with nine volumes of ethanol, and portions from the supernate were used in the assays. The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates. 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 3.2 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +/- SD) of the bile acid conjugates in serum from apparently healthy women and men (in mumol/L) were: cholic acid conjugates, 0.43 +/- 0.17 (n = 126); chenodeoxycholic acid conjugates, 0.47 +/- 0.23 (n = 111); and deoxycholic acid conjugates, 0.33 +/- 0.11 (n = 96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases.

Topics: Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Female; Hepatitis; Humans; Liver Cirrhosis; Male; Pregnancy; Pregnancy Complications; Radioimmunoassay

Topics: Animals; Cholestasis; Cholic Acids; Cytochrome Reductases; Deoxycholic Acid; In Vitro Techniques; Lipid Metabolism; Male; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Oxygenases; Rats; Taurocholic Acid; Taurodeoxycholic Acid

Topics: Calcium; Chemical and Drug Induced Liver Injury; Chenodeoxycholic Acid; Cholangitis; Cholecystectomy; Cholecystitis; Cholelithiasis; Cholestasis; Cholesterol; Deoxycholic Acid; Humans

Serum concentrations of cholic (C), chenodeoxycholic (CD) and deoxycholic (D) acids were determined both in the fasting state and after a meal using a gas chromatographic method in 14 patients with cholestasis of pregnancy. A significant rise was found in the levels of all these three bile acids, especially of C and CD. The peak level occurred 60 minutes to 3 hours from the beginning of the meal. Fasting and postprandial bile acid levels in the patients were compared with those obtained in a control group of 13 pregnant women without any evidence of disturbed maternal liver function. In the cholestasis cases, the values, especially of C, were highly elevated and increased more after the meal than in the control group. Measurement of postprandial levels of serum bile acids gives further confirmation of the presence of cholestasis particularly in those pregnant patients with a suspected disturbance in liver function whose fasting bile acid levels are only slightly elevated.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bile Acids and Salts; Bilirubin; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Fasting; Female; Humans; Pregnancy; Pregnancy Complications

The effect of phospholipase A from snake venom and deoxycholic acid on lipoprotein-X (LP-X) recovered from the cathode side of a previous agar gel electrophoresis is described. Adding phospholipase A and deoxycholic acid to the removed cathodal fraction is followed by a marked migration to the anode side on a second electrophoresis procedure. This seems to confirm that phospholipase A and bile salts on LP-X particles modifying their agar gel electrophoretic migration characteristics.

Topics: Cholestasis; Deoxycholic Acid; Electrophoresis, Agar Gel; Humans; Lipoproteins, LDL; Phospholipases

Deoxycholic acid conjugation, transport capacity, and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats were found to have a lower capacity to transport deoxycholic acid than taurodeoxycholic acid, and both were decreased by ethinyl estradiol treatment. During [24-14C]sodium deoxycholate infusion, [14C]biliary bile acid secretion increased, but bile flow did not change significantly in either control or ethinyl estradiol-treated rats. Ethinyl estradiol-treated animals excreted significantly less 14C as taurocholic acid than did control animals, consistent with an impairment of 7alpha-hydroxylation of taurodeoxycholic acid. Ethinyl estradiol treatment did not impair conjugation of deoxycholic acid, but did result in an increase in sulfation of taurodeoxycholic acid from 1.5% in controls to nearly 4.0% (P less than 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. Furthermore, the rat converts deoxycholic acid, a poor choleretic, to taurocholic acid, a good choleretic. When this conversion is impaired with ethinyl estradiol treatment, sulfation may be an important alternate pathway for excretion of this potentially harmful bile acid.

Topics: Animals; Carbon Radioisotopes; Cholestasis; Deoxycholic Acid; Ethinyl Estradiol; Hydroxylation; Liver; Male; Rats

To define the relationship of bile acid retention to the pruritus of cholestasis, we quantified individual bile acids in serum, acetone swabs of skin, and skin tissue in 13 patients with cholestasis undergoing laparotomy and in 8 controls. There was no consistent relationship between pruritus and concentrations of either total or individual bile acids in serum. Skin tissue concentrations of bile acids were elevated in patients with cholestasis, were linearly related to serum levels, and did not differentiate between those patients with and those without pruritus. Concentrations of bile acids on the skin surface, which were lower than those reported by others, did not correlate with pruritus, and were decreased by simple soap and water washing. These data indicate that the pruritus of cholestasis is not directly related to the skin tissue concentration of any of the major bile acids, although a relationship to a particular molecular form of bile acids could not be excluded.

Topics: Adult; Aged; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Deoxycholic Acid; Female; Humans; Lithocholic Acid; Male; Middle Aged; Pruritus; Skin

A sensitive radioimmunoassay for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine was established using antibodies obtained from rabbits injected with albumin conjugates of these bile acids. Glycine-conjugated bile acid levels were measured in sera from 25 control subjects and 110 patients who had hepatic disease (alcoholic cirrhosis, hepatitis, cholestasis, and hepatic malignancy). Sulfolithocholylglycine was elevated in the sera of all 110 patients with hepatic disease. Cholylglucine was within normal range in only three. Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy. It was normal in most sera of patients who had alcoholic cirrhosis, suggesting that chenodeoxycholic acid may be subject to further biotransformations in these patients. Deoxycholylglycine was elevated in a minority of patients, none of whom had cholestasis. The data suggest that serum bile acids, particularly sulfolithocholylglycine, are a highly sensitive index for hepatic dysfunction.

Topics: Alcoholism; Biliary Tract Diseases; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Glycocholic Acid; Hepatitis; Humans; Lithocholic Acid; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Radioimmunoassay

Large amounts of bile acid sulfate were found in the urine of patients with hepatobiliary diseases. In patients with acute hepatitis, daily excretion of bile acid into urine was 68.24 plus or minus 51.80 mumoles per day, and the percentage of sulfated bile acid was 83.4 plus or minus 16.7%. In patients with chronic hepatitis and cirrhosis, a slight increase of urinary bile acid was observed (2.89 plus or minus 2.69 and 5.27 plus or minus 4.28 mumoles per day, respectively), and the percentage of sulfated bile acid was 73.9 plus or minus 28.6 and 44.6 plus or minus 30.4%, respectively. In patients with obstructive jaundice, a moderate increase of urinary bile acid was found (32.62 plus or minus 18.35 mumoles per day), and the percentage of sulfated bile acid was 58.3 plus or minus 22.6%. In patients with hepatobiliary diseases, the elevation of both levels of sulfated and nonsulfated bile acids in serum was observed. The percentage of sulfated bile acid was 9% in normal serum, and varied from zero to 82.8% in pathological sera. A remarkable increase of sulfated bile acid was found in patients with obstructive juandice and acute hepatitis, while a slight elevation was found in patients with chronic hepatitis and cirrhosis. Sulfated bile acid in bile was nonexistent or below 0.5% of total bile acid. According to these findings, the increased bile acid in serum of patients with hepatobiliary diseases might be more easily excreted into the urine as sulfated bile acid.

Topics: Bile Acids and Salts; Biliary Tract Diseases; Carbon Radioisotopes; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chromatography, Gas; Deoxycholic Acid; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Male; Sulfates

Topics: Bile Acids and Salts; Cholestasis; Deoxycholic Acid; Humans; Hydroxycholesterols; Hydroxylation

Bile acids were extracted from serum samples by chromatography on Amberlite XAD-2 and, after alkaline or enzymic hydrolysis, purified by chromatography on aluminium oxide. The quantitation was carried out by gas-liquid chromatography with an OV-101 glass capillary column using their methyl ester trimethylsilyl derivatives. The mean total amount of cholic, chenodeoxycholic and deoxycholic acids in a group of healthy fasting women was 2.14 mumol/l, in a group of fasting pregnant women at 8-12 weeks of gestation 1.13 mumol/l and at 38-41 weeks of gestation 2.10 mumol/l. In patients with cholestasis of pregnancy the total bile acid levels varied from 6 to 86 mumol/l.

Topics: Adult; Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chromatography, Gas; Deoxycholic Acid; Female; Gestational Age; Humans; Pregnancy; Pregnancy Complications

Morphologic alterations in liver cells after bile duct ligation are well known and documented in numerous reports. Biochemical studies concerning metabolic changes in cholestatic liver are rare. Therefore, in this study, liver cell metabolites and the capacity of the perfused cholestatic rat liver to produce glucose, urea and ketone bodies were measured. In addition the influence of dihydroxy bile acids on normal and bile duct ligated rat livers was studied. Concentrations of adenine nucleotides, lactate, pyruvate, 3-hydroxybutyrate, acetoacetate, glucose and UDP-glucose were found to be identical in cholestatic and normal livers. Glycogen content, however, was significantly lowered in cholestatic livers. Gluconeogenesis from lactate and urea production from ammonium chloride were only slightly reduced in bile duct obstructed rat livers. Dihydroxy bile acids did not affect the metabolism of normal or cholestatic livers. Ketone body production from oleate was reduced to 66% in bile duct obstructed livers, taurochenodeoxycholate further reduced this value to the normal value. In contrast to earlier reports (Fisher and co-workers, 1971 Lab. Invest. 21; 88-91; Gastroenterology 60: 742) chenodeoxycholate induced neither cholestasis nor a marked fall in ATP content or rat liver in our experiments with female Wistar rats. In conclusion, dihydroxy bile salts did exert toxic short term effects on rat livers.

Topics: Acetoacetates; Adenine Nucleotides; Animals; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Common Bile Duct; Deoxycholic Acid; Female; Gluconeogenesis; Glycogen; Hydroxybutyrates; Ketone Bodies; Ligation; Liver; Male; Rats; Urea

The pruritic effect of purified bile salts has been tested by applying them to blister bases. All the salts tested were pruritogens, but the dihydroxy salts (especially unconjugated chenodeoxycholate) were more effective than the trihydroxy salts. This may explain the poor correlation between total serum bile salt concentration and pruritus in obstructive jaundice.

Topics: Adolescent; Adult; Aged; Bile Acids and Salts; Blister; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Deoxycholic Acid; Female; Humans; Male; Middle Aged; Pruritus; Skin Tests

Topics: Animals; Bile Acids and Salts; Cholestasis; Cholic Acids; Cytochrome P-450 Enzyme System; Deoxycholic Acid; Hydroxylation; Microsomes, Liver; Rats; Taurocholic Acid

Topics: Acute Disease; Adolescent; Adult; Aged; Bile Acids and Salts; Cholelithiasis; Cholestasis; Chromatography, Gas; Chromatography, Ion Exchange; Deoxycholic Acid; Hepatitis A; Humans; Jaundice; Lithocholic Acid; Mass Spectrometry; Middle Aged

Topics: Animals; Bile Acids and Salts; Bile Ducts; Biliary Tract Diseases; Biopsy; Biotransformation; Carbon Radioisotopes; Cholestasis; Cholesterol; Cholic Acids; Chromatography, Gas; Chromatography, Thin Layer; Deoxycholic Acid; Feces; Humans; Lithocholic Acid; Liver; Liver Cirrhosis; Microsomes, Liver; Mitochondria, Liver; Rats

Topics: Bile Acids and Salts; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chronic Disease; Deoxycholic Acid; Hepatic Encephalopathy; Hepatitis; Humans; Lithocholic Acid; Liver Cirrhosis; Liver Diseases

Topics: Adult; Aged; Bile Acids and Salts; Biliary Tract Diseases; Chenodeoxycholic Acid; Cholestasis; Cholic Acids; Chromatography, Gel; Chromatography, Ion Exchange; Deoxycholic Acid; Female; Glycocholic Acid; Humans; Liver Diseases; Liver Function Tests; Male; Middle Aged; Sulfuric Acids; Taurocholic Acid