Search results for " Salts"
showing 10 items of 200 documents
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 …
Inactivation of glycogen synthase kinase-3β protects against kainic acid-induced neurotoxicity in vivo
2004
Many neurodegenerative diseases involve oxidative stress and excitotoxic cell death. In an attempt to further elucidate the signal transduction pathways involved in the cell death/cell survival associated with excitotoxicity, we have used an in vivo model of excitotoxicity employing kainic acid (KA)-induced neurotoxicity. Here, we show that extracellular signal-related kinase (ERK) 2, but not ERK 1, is phosphorylated and thereby activated in the hippocampus and cerebellum of kainic acid-treated mice. Phosphorylation and hence inactivation of glycogen synthase kinase 3beta (GSK-3beta), a general survival factor, is often a downstream consequence of mitogen-activated protein kinase pathway ac…
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…
Glycogen synthase kinase 3β links neuroprotection by 17β-estradiol to key Alzheimer processes
2004
Estrogen exerts many of its receptor-mediated neuroprotective functions through the activation of various intracellular signal transduction pathways including the mitogen activating protein kinase (MAPK), phospho inositol-3 kinase and protein kinase C pathways. Here we have used a hippocampal slice culture model of kainic acid-induced neurotoxic cell death to show that estrogen can protect against oxidative cell death. We have previously shown that MAPK and glycogen synthase kinase-3beta (GSK-3beta) are involved in the cell death/cell survival induced by kainic acid. In this model and other cellular and in vivo models we have shown that estrogen can also cause the phosphorylation and hence …
An insight into the functionalisation of carbon nanotubes by diazonium chemistry: Towards a controlled decoration
2014
The derivatisation of materials including iron, gold, and carbon by addition of diazonium salts is a reliable process to tune their interfacial interaction with the surrounding media. In this regard, the functionalisation of carbon nanostructures by diazonium chemistry is a versatile strategy to obtain soluble nanomaterials with degrees of functionalisation among the highest ever reported. Starting from these premises we have studied the functionalisation of multi-walled carbon nanotubes by addition of the aryl diazonium salts generated in situ by treatment of 4-methoxyaniline with isopentylnitrite. Following a thorough purification and characterisation protocol (UV-vis, TGA, ATR-IR, cyclic…