-
Chemical & Pharmaceutical Bulletin May 2009Two new bile acids, tauroselocholic acid (1) and tauroansocholic acid (2), a new natural bile acid, cygnocholic acid (3) were respectively isolated from bear bile powder...
Two new bile acids, tauroselocholic acid (1) and tauroansocholic acid (2), a new natural bile acid, cygnocholic acid (3) were respectively isolated from bear bile powder Selenaretos thibetanus CUVIER and bile of geese Anser anser domesticus, together with seven known compounds. By spectrum analysis of MS, 1D and 2D NMR, the structures of the new compounds were elucidated as 3alpha,7alpha,9alpha-trihydroxy-5beta-cholan-24-oic acid N-[2-sulfoethyl] amide (1), 3alpha,5,7alpha-trihydroxy-5beta-cholan-24-oic acid N-[2-sulfoethyl] amide (2) and 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid (3).
Topics: Animals; Bile; Bile Acids and Salts; Cholic Acids; Geese; Magnetic Resonance Spectroscopy; Molecular Structure; Powders; Ursidae
PubMed: 19420790
DOI: 10.1248/cpb.57.528 -
Journal of Korean Medical Science Jul 2021Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully....
BACKGROUND
Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis.
METHODS
We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants.
RESULTS
No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions.
CONCLUSION
We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including , in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.
Topics: Adult; Bacteria; Bile; Case-Control Studies; Cholecystitis; Dysbiosis; Gallbladder; Gallbladder Diseases; Gallbladder Neoplasms; Humans; Metagenomics; Microbiota; Middle Aged; Phylogeny
PubMed: 34282606
DOI: 10.3346/jkms.2021.36.e189 -
Biochimica Et Biophysica Acta.... Mar 2019Long-chain acyl-CoA synthetase 1 (ACSL1) plays a pivotal role in fatty acid β‑oxidation in heart, adipose tissue and skeletal muscle. However, key functions of ACSL1...
Identification of a novel function of hepatic long-chain acyl-CoA synthetase-1 (ACSL1) in bile acid synthesis and its regulation by bile acid-activated farnesoid X receptor.
Long-chain acyl-CoA synthetase 1 (ACSL1) plays a pivotal role in fatty acid β‑oxidation in heart, adipose tissue and skeletal muscle. However, key functions of ACSL1 in the liver remain largely unknown. We investigated acute effects of hepatic ACSL1 deficiency on lipid metabolism in adult mice under hyperlipidemic and normolipidemic conditions. We knocked down hepatic ACSL1 expression using adenovirus expressing a ACSL1 shRNA (Ad-shAcsl1) in mice fed a high-fat diet or a normal chow diet. Hepatic ACSL1 depletion generated a hypercholesterolemic phenotype in mice fed both diets with marked elevations of total cholesterol, LDL-cholesterol and free cholesterol in circulation and accumulations of cholesterol in the liver. Furthermore, SREBP2 pathway in ACSL1 depleted livers was severely repressed with a 50% reduction of LDL receptor protein levels. In contrast to the dysregulated cholesterol metabolism, serum triglycerides, free fatty acid and phospholipid levels were unaffected. Mechanistic investigations of genome-wide gene expression profiling and pathway analysis revealed that ACSL1 depletion repressed expressions of several key enzymes for bile acid biosynthesis, consequently leading to reduced liver bile acid levels and altered bile acid compositions. These results are the first demonstration of a requisite role of ACSL1 in bile acid biosynthetic pathway in liver tissue. Furthermore, we discovered that Acsl1 is a novel molecular target of the bile acid-activated farnesoid X receptor (FXR). Activation of FXR by agonist obeticholic acid repressed the expression of ACSL1 protein and mRNA in the liver of FXR wild-type mice but not in FXR knockout mice.
Topics: Animals; Bile; Bile Acids and Salts; Cholesterol; Coenzyme A Ligases; Diet, High-Fat; Lipid Metabolism; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Cytoplasmic and Nuclear; Receptors, LDL
PubMed: 30580099
DOI: 10.1016/j.bbalip.2018.12.012 -
Journal of Lipid Research Jan 1979Quantitative analyses of individual bile acids in biological samples are limited by the lengthy multistep preparations necessary. Using heptafluorobutyric acid anhydride... (Comparative Study)
Comparative Study
Quantitative analyses of individual bile acids in biological samples are limited by the lengthy multistep preparations necessary. Using heptafluorobutyric acid anhydride in pyridine as derivatizing agent, we reduced several steps to one. Bile acids and their glycine and taurine conjugates form stable heptafluorobutyrate derivatives, climinating the need for deconjugation and preparation of methyl esters. The derivatives have been characterized by mass spectrometry, and optimum reaction yields have been determined. Operating conditions for analyzing the bile acid heptafluorobutyrates by gas-liquid chromatography on various column packings were investigated, and 0.5% QF-1 or 3% OV-255 was found suitable. The bile acid derivatives were identical whether starting with the bile acid or the glycine or taurine conjugates. The procedure was applied to a quantitative analysis of artificial mixtures of bile acids and bile conjugates, and also of human bile. The results compared favorably to those obtained with a 3 alpha- and 7 alpha-hydroxysteroid dehydrogenase fluorimetric method.
Topics: Bile; Bile Acids and Salts; Butyrates; Cholelithiasis; Chromatography, Gas; Female; Fluorocarbons; Humans; Hydroxysteroid Dehydrogenases; Male; Mass Spectrometry; Spectrometry, Fluorescence
PubMed: 438655
DOI: No ID Found -
Revista de Gastroenterologia de Mexico... 2020Normally, the bile ducts are sterile, but up to 4.2% of healthy persons can present with positive cultures. Certain circumstances favor that situation, such as...
INTRODUCTION AND AIM
Normally, the bile ducts are sterile, but up to 4.2% of healthy persons can present with positive cultures. Certain circumstances favor that situation, such as gallstones or biliary tree manipulation. The aim of the present study was to determine the factors that influence the presence of bacteriobilia, as well as its implications for clinical practice.
MATERIALS AND METHODS
A prospective study was conducted on bile cultures from patients that underwent cholecystectomy at our hospital center within the time frame of 2013 to 2015.
RESULTS
The study included 196 patients (42.3% women and 57.7% men) that underwent either open or laparoscopic cholecystectomy and in whom bile fluid samples were taken. The clinical, epidemiologic, and laboratory test characteristics of the patients were analyzed, as well as the surgical indication (urgent surgery or programmed surgery). With respect to microbiology, 47% of the bile cultures were positive: 56.5% presented with one microorganism, 25% with two, and 18.5% with three or more.
CONCLUSION
Microbiologic bile analysis should not be systematically performed, given that its result is relevant only in cases that present with demonstrated risk factors. However, in those cases, said analysis is essential to establish adequate antibiotic treatment, in relation to activity spectrum and duration, to prevent complications and an increase in microbial resistance.
Topics: Adult; Aged; Bile; Cholecystectomy; Female; Humans; Male; Middle Aged; Prospective Studies
PubMed: 32019715
DOI: 10.1016/j.rgmx.2019.07.006 -
The Journal of Medical Investigation :... 2012Bile and pancreatic juice contain a number of parameters for cancer chemoprevention. Indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC), which are hydrolytic...
Bile and pancreatic juice contain a number of parameters for cancer chemoprevention. Indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC), which are hydrolytic products of brassica plants, have been established to be anti-cancer agents. Here, we developed a method for the continuous and selective sampling of bile and pancreatic juice, and the effects of I3C and PEITC on bile and pancreatic excretion and γ-glutamyl transpeptidase (γ-GTP) activity in the samples were investigated. Male Fisher 344 rats (eight weeks of age) were challenged intragastrically with I3C (150 mg/kg) or PEITC (160 mg/kg) for five days. Twenty-four hours after the final administration, cannulation was undertaken into the rats' bile and pancreatic ducts, and the bile and pancreatic juice were separately collected for 48 h. In this rat model, bile was stably excreted, and the bile and pancreatic excretion of the control rats was 21.9 ± 1.4 ml/48 h and 12.8 ± 1.7 ml/48 h, respectively. Bile excretion for the first 24 h significantly increased in the I3C- or PEITC-treated rats compared with the control rats. In the case of pancreatic juice, excretion during the first 24 h significantly increased in the PEITC-treated rats. In bile, γ-GTP activity was significantly increased for the first 24 h in the I3C- and PEITC-treated rats, but no difference was observed in the pancreatic juice. Increases of bile excretion and γ-GTP activity in bile might be a factor involved in the anti-cancer effect of I3C and PEITC. Our rat model described here is a useful tool for the study of cancer chemoprevention.
Topics: Animals; Anticarcinogenic Agents; Bile; Indoles; Isothiocyanates; Male; Pancreatic Juice; Rats; Rats, Inbred F344; gamma-Glutamyltransferase
PubMed: 23037195
DOI: 10.2152/jmi.59.246 -
Annals of Hepatology 2008Oxidative stress is a common feature in most hepatopathies. In recent years, evidence has accumulated that reactive oxygen species (ROS) induce a number of functional... (Review)
Review
Oxidative stress is a common feature in most hepatopathies. In recent years, evidence has accumulated that reactive oxygen species (ROS) induce a number of functional changes either deleterious or adaptive in the capability of the hepatocytes to produce bile and to secrete exogenous and endogenous compounds. This review is aimed to describe the mechanisms involved in these alterations. For this purpose, we will summarize: 1) The current evidence that acutely-induced oxidative stress is cholestatic, by describing the mechanisms underlying the hepatocyte secretory failure, including the disorganization of the actin cytoskeleton and its most noticeable consequences, the impairment of tight-junctional structures and the endocytic internalization of canalicular transporters relevant to bile formation. 2) The role for oxidative-stress-activated signalling pathways in the pathomechanisms described above, particularly those involving Ca2+ elevation and its consequent activation of Ca2+ -dependent PKC isoforms. 3) The mechanisms involved in the adaptive response against oxidative stress mediated by ROS-responsive transcription factors, involving up-regulation of GSH-synthesizing enzymes, GSH-detoxifying enzymes and the hepatocellular efflux pumps; this response enhances the co-coordinated inactivation by GSH conjugation of lipid peroxides and their further cellular extrusion. 4) The manner this adaptive response can be surpassed by the sustained production of ROS, thus inducing transcriptional and posttranscriptional changes in transporters relevant to bile formation, as has been shown to occur, for example, after long-term administration of aluminum to rats, in the Long-Evans Cinnamon rat (a model of chronic hepatic copper accumulation mimicking Wilson's disease), and in ischemia-reperfusion injury.
Topics: Animals; Bile; Biliary Tract; Biliary Tract Diseases; Humans; Liver; Liver Diseases; Oxidative Stress
PubMed: 18376363
DOI: No ID Found -
Scientific Reports Oct 2022Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of intra- and extrahepatic...
Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of intra- and extrahepatic bile ducts. Osteoporosis is a frequent comorbidity in PSC, and we could previously demonstrate that IL17-dependent activation of bone resorption is the predominant driver of bone loss in PSC. Since we additionally observed an unexpected heterogeneity of bone mineral density in our cohort of 238 PSC patients, the present study focused on a comparative analysis of affected individuals with diagnosed osteoporosis (PSC, n = 10) or high bone mass (PSC, n = 7). The two groups were not distinguishable by various baseline characteristics, including liver fibrosis or serum parameters for hepatic function. In contrast, quantification of serum bile acid concentrations identified significant increases in the PSC group, including glycoursodeoxycholic acid (GUDCA), an exogenous bile acid administered to both patient groups. Although cell culture experiments did not support the hypothesis that an increase in circulating bile levels is a primary cause of PSC-associated osteoporosis, the remarkable differences of endogenous bile acids and GUDCA in the serum of PSC patients strongly suggest a yet unknown impairment of biliary metabolism and/or hepatic bile acid clearance in this patient subgroup, which is independent of liver fibrosis.
Topics: Bile; Bile Acids and Salts; Cholangitis, Sclerosing; Humans; Liver Cirrhosis; Osteoporosis
PubMed: 36192408
DOI: 10.1038/s41598-022-20351-z -
PLoS Neglected Tropical Diseases Apr 2020Clonorchiasis, caused by chronic infection with Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease that seriously afflicts more than 35...
Clonorchiasis, caused by chronic infection with Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease that seriously afflicts more than 35 million people globally, resulting in a socioeconomic burden in endemic regions. C. sinensis adults long-term inhabit the microaerobic and limited-glucose environment of the bile ducts. Energy metabolism plays a key role in facilitating the adaptation of adult flukes to crowded habitat and hostile environment. To understand energy source for adult flukes, we compared the component and content of free amino acids between C. sinensis-infected and uninfected bile. The results showed that the concentrations of free amino acids, including aspartic acid, serine, glycine, alanine, histidine, asparagine, threonine, lysine, hydroxylysine, and urea, were significantly higher in C. sinensis-infected bile than those in uninfected bile. Furthermore, exogenous amino acids could be utilized by adult flukes via the gluconeogenesis pathway regardless of the absence or presence of exogenous glucose, and the rate-limiting enzymes, such as C. sinensis glucose-6-phosphatase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and pyruvate carboxylase, exhibited high expression levels by quantitative real-time PCR analysis. Interestingly, no matter whether exogenous glucose was present, inhibition of gluconeogenesis reduced the glucose and glycogen levels as well as the viability and survival time of adult flukes. These results suggest that gluconeogenesis might play a vital role in energy metabolism of C. sinensis and exogenous amino acids probably serve as an important energy source that benefits the continued survival of adult flukes in the host. Our study will be a cornerstone for illuminating the biological characteristics of C. sinensis and the host-parasite interactions.
Topics: Amino Acids; Animals; Bile; Cats; Clonorchiasis; Clonorchis sinensis; Disease Models, Animal; Energy Metabolism; Gene Expression Profiling; Gluconeogenesis; Metabolic Networks and Pathways; Rats
PubMed: 32352979
DOI: 10.1371/journal.pntd.0008287 -
Frontiers in Bioscience (Landmark... Jan 2012Vectorial transport of osmotically active solutes from blood into bile is essential for bile flow generation. Therefore, the localization status of hepatocellular... (Review)
Review
Vectorial transport of osmotically active solutes from blood into bile is essential for bile flow generation. Therefore, the localization status of hepatocellular transporters involved in this function is critical. These transporters are localized either in the plasma membrane or in an endosomal, submembranous compartment, from where they undergo recycling to the plasma membrane. The balance between exocytic targeting/endocytic internalization from/to this recycling compartment is therefore a chief determinant of the liver capability to secrete bile. Furthermore, its impairment may lead to sustained endocytic internalization, eventually resulting in transporter degradation. Exacerbated internalization of hepatocellular transporters occurs in several experimental models of cholestasis, and also in most human cholestatic liver diseases. This review outlines the possible mechanisms explaining this alteration (e.g., alteration of the organization of actin or actin-transporter linking proteins), and the mediators involved (e.g., activation of "cholestatic" signaling pathways). Finally, several experimental therapeutic approaches based upon the administration of compounds that stimulate exocytic targeting of canalicular transporters (e.g., cAMP, tauroursodeoxycholate) are described with regard to their capability to prevent cholestatic alterations resulting from transporter internalization.
Topics: Bile; Carrier Proteins; Cholestasis; Humans
PubMed: 22201798
DOI: 10.2741/3981