Search results for "Bile acids and salts"
showing 10 items of 56 documents
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: A potential role for bile acids
2017
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG), and suppressing the gut bacteria via chronic oral administration of antibiotics. GG feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, GG enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid l…
Effects of peroxisome proliferator-activated receptor alpha activation on pathways contributing to cholesterol homeostasis in rat hepatocytes
2004
International audience; Peroxisome proliferator-activated receptor alpha (PPARa) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investigated in parallel the changes in the metabolic pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with cholesterogenesis from [14C] acetate and [3H] mevalonate. The up-regulation observed in fenofibrate- and WY-14,643-treate…
Fluorescent benzofurazan-cholic acid conjugates for in vitro assessment of bile acid uptake and its modulation by drugs.
2009
One of the most common mechanisms of hepatotoxicity is drug-induced cholestasis. Hence, new approaches for screening the cholestatic potential of drug candidates are desirable. In this context, we describe herein the use of synthetic 4-nitrobenzo-2-oxa-1,3-diazole (NBD) fluorescent conjugates of cholic acid (ChA) at positions 3alpha, 3beta, 7alpha, and 7beta for in vitro assessment of bile acid uptake. All the conjugates show a strong absorption band between 400 and 550 nm and have a fluorescence quantum yield of approximately 0.45, with an emission maximum centered at approximately 530 nm. After their photophysical characterization, 3alpha-, 3beta-, 7alpha-, and 7beta-NBD-ChA were used to …
Effects of a preparation containing a standardized ginseng extract combined with trace elements and multivitamins against hepatotoxin-induced chronic…
1987
A preparation containing a standardized ginseng extract which has been shown to exert anti-hepatotoxic activity in vitro, combined with trace elements and multi-vitamins was compared to placebo in 24 elderly out-patients with toxin-induced (alcohol and drugs) chronic liver disease in order to evaluate its effect on liver function. Each patient was blindly treated either with the preparation containing ginseng extract or placebo for 12 weeks. The preparation containing ginseng extract significantly modified bromsulphthalein retention and blood zinc levels when compared to pre-treatment levels and to placebo. Serum bile acids, and γ-glutamyl transpeptidase before and after a fatty meal were …
Ion Pairing with Bile Salts Modulates Intestinal Permeability and Contributes to Food–Drug Interaction of BCS Class III Compound Trospium Chloride
2013
In the current study the involvement of ion pair formation between bile salts and trospium chloride (TC), a positively charged Biopharmaceutical Classification System (BCS) class III substance, showing a decrease in bioavailability upon coadministration with food (negative food effect) was investigated. Isothermal titration calorimetry provided evidence of a reaction between TC and bile acids. An effect of ion pair formation on the apparent partition coefficient (APC) was examined using (3)H-trospium. The addition of bovine bile and bile extract porcine led to a significant increase of the APC. In vitro permeability studies of trospium were performed across Caco-2-monolayers and excised seg…
Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method
2012
Bile acids (BAs) are a group of chemically related steroids recognized as regulatory molecules whose profiles can change in different physio-pathological situations. We have developed a sensitive, fast, and reproducible ultraperformance liquid chromatography/multiple reaction monitoring/mass spectrometry method to determine the tissue and sera BA profiles in different species (human, rat, and mouse) by quantifying 31 major and minor BA species in a single 21-min run. The method has been validated according to FDA guidelines, and it generally provides good results in terms of intra- and interday precision (less than 8.6% and 16.0%, respectively), accuracy (relative error measurement between …
Presence of white bile in malignant biliary obstruction is associated with poor prognosis: personal preliminary observations
2006
OBJECTIVE: The chemical composition and clinical significance of white bile in patients with malignant obstructive jaundice were evaluated in a prospective study. MATERIALS AND METHODS: 115 consecutive patients with inoperable malignant biliary obstruction underwent endoscopic placement of 10 Fr straight, plastic biliary stents, Amsterdam-type. Bile was aspirated during the endoscopic procedure and a blood sample was taken. Patients were divided into two groups: those with white bile and those with yellow bile. The groups were compared for decremental fall in bilirubin, cholangitis after stent insertion, and survival. RESULTS: Thirty-five patients (15 men, 20 women; mean age 54 years) under…
Functional, Biochemical, and Morphological Hepatobiliary Effects in Rats Chronically Exposed to a Steroidal Antiandrogen
1996
Abstract Yellow–brown deposits in intrahepatic bile ducts and portal macrophages were observed for male, but not female, Sprague–Dawley rats fed zanoterone, a steroidal antiandrogen, for ≥3 months. The lesion did not affect biliary canaliculi and was associated with changes of biliary epithelium, portal chronic inflammation, and bile duct proliferation. Deposit formation was assumed to be related to a gender-related anomaly in bile composition and/or flow. Therefore, the pathogenesis of the lesion was investigated in male, female, and orchiectomized rats. Hepatobiliary structure and function were evaluated after 3 months of treatment and 3 months of reversibility. Drug biliary disposition w…
Deficiency of bile acid transport and synthesis in oval cells from carcinogen-fed rats.
1994
Freshly isolated oval cells, which we obtained from the livers of rats fed a choline-deficient/DL-ethioninesupplemented diet, did not transport bile acids. Compared with freshly isolated rat hepatocytes they took up only negligible amounts of [3H]taurocholate or [14C]cholate. The cells bound small amounts of radioactive bile acids. This portion of the total cell-associated radioactivity was enhanced on membrane permeabilization. In contrast to cultured liver parenchymal cells from untreated rats, no bile acid synthesis was detected in cultured oval cells. Cultured oval cells also lost the ability to conjugate exogenously added cholate (100 μmol/L) with taurine or glycine. However, when live…
Structural studies of five novel bile acid-4-aminopyridine conjugates
2012
Abstract Synthesis and solid-state structural characterization of five bile acid amides of 4-aminopyridine (4-AP) are reported. Systematic crystallization experiments revealed a number of structural modifications and/or solvate/hydrate systems for these conjugates. Particularly, cholic acid conjugate exhibited five distinct structure modifications, including one anhydrous form, mono- and dihydrates, as well as ethanol and 2-butanol solvates. The obtained crystal forms were examined extensively with various analytical methods, including solid-state NMR, Raman, and IR spectroscopies, powder and single crystal X-ray diffraction methods, thermogravimetry, and differential scanning calorimetry. …