• NTCP and ASBT are cotransporters that mediate sodium-dependent, electrogenic uptake of mainly bile salts into hepatocytes (NTCP), biliary epithelial cells, ileal enterocytes and renal proximal The importance of membrane voltage in uptake of bile salts into hepatocytes is not known. (web.app)
  • While expression of NTCP is restricted to 1987-03-30 The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. (web.app)
  • ASBT is Na-dependent uptake transporter of bile acids and conjugates. (web.app)
  • A cDNA encoding the rat liver bile acid uptake system has been isolated by expression cloning in Xenopus laevis oocytes. (web.app)
  • Some studies suggest that an increase in plasma fatty acid concentration reduces glucose uptake and phosphorylation, and this leads to reduced glycogen synthesis and glucose oxidation. (heraldopenaccess.us)
  • Peer reviewer: and fatty acids, which together with bile salts, lysophospholipids, and un- absorbed by facilitated diffusion that does not involve sodium co-transport. (web.app)
  • EMD 56133 did not interfere with transport systems for monovalent organic cations, amino acids and long chain fatty acids. (nih.gov)
  • Several substrates of other endogenous transport systems (e.g. bilirubin, cyclopeptides, monovalent cations, dipeptides, amino acids, fatty acids, hexoses) did not interfere with the transport of EMD 56133. (nih.gov)
  • In addition, there is evidence that fatty acids interfere with very early stages of Glucose Transporter Type 4 (GLUT4) and hexokinase II activity [8]. (heraldopenaccess.us)
  • Carnitine plays a role in the transfer of long chain fatty acids from cytoplasm to mitochondria for beta-oxidation. (heraldopenaccess.us)
  • It plays an important role in alleviating the impact of cholestasis on hepatocytes by effluxing bile acids into the blood, and can be up-regulated in the liver in such instances. (solvobiotech.com)
  • Lägga till sterila PEG 8000 i fosfatbuffrad saltlösning (PBS) insamlade medellång till en Kinetics of the bile acid transporter and hepatitis B virus receptor Na+/taurocholate cotransporting polypeptide (NTCP) in hepatocytes. (web.app)
  • MRP4 has long been known to require reduced glutathione for the transport of bile acids [20], but the MRP4-mediated extrusion of other substrates such as halobenzoquinones may also depend on GSH, possibly via conjugate formation [21]. (solvobiotech.com)
  • Two series of biphenyl carboxylic acids were designed based on the structures of URAT1 inhibitors Epaminurad and Telmisartan via a strategy of pharmacophore fusion. (bvsalud.org)
  • Increased plasma free fatty acid concentration is associated with insulin resistance. (heraldopenaccess.us)
  • Computer, principal coordinate.Intestinal Fucosylation in Steatohepatitisresult within a decreased bile acid pool size by activating intestinal FXR PAK5 medchemexpress signaling pathways and growing fecal excretion of bile acids. (calpaininhibitor.com)
  • On the other hand, the activation of FXR failed to Toxoplasma MedChemExpress inhibit bile acid synthesis in our Western diet program ed WT mice. (calpaininhibitor.com)
  • ens Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile acid cotransporter) (Na+ Sodium as salt and Potassium expert: Antti Jula, Finland. (web.app)
  • It has an important physiological function as the first step in bile acid (BA) reabsorption from the intestine, playing a key role in the enterohepatic recirculation of BAs [1]. (web.app)
  • The cloned transporter is strictly sodium-dependent and can be inhibited by various non-bile-acid organic compounds. (web.app)
  • Up to 10 different MDR3 mutations have been identified and any one of these mutations may result in loss of function and, therefore, raise bile acid levels. (medscape.com)
  • The adverse feedback mechanism by way of FXR/Fgf15 inhibits transcription of Cyp7a1 in hepatocytes and limits de novo synthesis of bile acids.52 Western diet plan ed WT mice had a larger amount of taurocholic acid (TCA) in the plasma (data not shown), which can act as an agonist of FXR and could contribute to increased serum FXR activity in these mice. (calpaininhibitor.com)
  • Affected individuals have a defect involving the excretion of bile salts, which leads to increased serum bile acids. (medscape.com)
  • Effect of islatravir on CYP mRNA in human hepatocytes. (caspaseinhibitor.com)
  • cardiopulmonary view poetry for students presenting analysis context of different scripts and surgical compounds of EN versus PN in human artery: a healthy diabetes and a heart. (ra-berg.de)
  • N improved principal to secondary ratio of fecal bile acids.49 In summary, adjustments inside the intestinal microbiota connected with Western diet ed Fut2-/- miceFigure eight. (calpaininhibitor.com)
  • Objective: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. (uni-muenchen.de)
  • Interestingly, these are also the bile acids significantly decreased by ursodeoxycholic acid (UCDA), which is currently the main pharmacological treatment. (medscape.com)
  • In sandwich-cultured rat hepatocytes, 10-min accumulation of taurocholate in cells + bile canaliculi (408 +/- 57 pmol/mg protein) was decreased significantly by troglitazone (157 +/- 17 pmol/mg protein, respectively) only in the presence of Na+, the driving force for the sodium taurocholate cotransporting polypeptide. (nih.gov)
  • 3. Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: role of glycine conjugates. (nih.gov)
  • 7. Use of cassette dosing in sandwich-cultured rat and human hepatocytes to identify drugs that inhibit bile acid transport. (nih.gov)
  • 8. Alpha-naphthylisothiocyanate modulates hepatobiliary transporters in sandwich-cultured rat hepatocytes. (nih.gov)
  • 10. Polygoni Multiflori Radix derived anthraquinones alter bile acid disposition in sandwich-cultured rat hepatocytes. (nih.gov)
  • 12. Combination lopinavir and ritonavir alter exogenous and endogenous bile acid disposition in sandwich-cultured rat hepatocytes. (nih.gov)
  • 18. An in vitro assay to assess transporter-based cholestatic hepatotoxicity using sandwich-cultured rat hepatocytes. (nih.gov)
  • Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat hepatocytes. (nih.gov)
  • In conclusion, xenobiotics may alter hepatic bile acid transport by inhibiting both hepatic uptake and biliary excretion. (nih.gov)
  • 4. Hepatobiliary disposition of troglitazone and metabolites in rat and human sandwich-cultured hepatocytes: use of Monte Carlo simulations to assess the impact of changes in biliary excretion on troglitazone sulfate accumulation. (nih.gov)
  • 9. Identification of Bile Acids Responsible for Inhibiting the Bile Salt Export Pump, Leading to Bile Acid Accumulation and Cell Toxicity in Rat Hepatocytes. (nih.gov)
  • Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. (biomedcentral.com)
  • 5. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis. (nih.gov)
  • In this regard, Myrcludex-B, a synthetic lipopeptide derived from pre-S1 domain of the HBV envelope protein, which specifically targets the NTCP has been shown to efficiently block HBV infection in in vitro [ 61 , 62 ] ]and in uPA/SCID mice reconstituted with human hepatocytes infected with HBV. (medscape.com)
  • Induction of phase I metabolic enzymes in SC rat hepatocytes to levels representative of in vivo expression and function may extend the utility of this in vitro model to facilitate the prediction of hepatobiliary disposition of metabolically labile substrates. (aspetjournals.org)
  • In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. (uni-muenchen.de)
  • Gene and protein expression and cellular localization were assessed in primary hepatocyte cultures (mouse and human) and cholestatic liver tissues (murine models and patients with primary biliary cholangitis [PBC] or primary sclerosing cholangitis [PSC]) by quantitative PCR, western blot and immunohistochemistry. (nih.gov)
  • The present studies examined the hypothesis that these xenobiotics may modulate multiple hepatic bile acid transport mechanisms. (nih.gov)
  • However, it is not known whether NFAT plays any role in the bile acid (BA)-induced hepatic inflammatory response. (nih.gov)
  • Treatment of SC rat hepatocytes with DEX resulted in alterations in the expression of CYP3A1/2 and some hepatic transport proteins. (aspetjournals.org)
  • Huss and Kasper, 2000 ) and a common medium supplement, on hepatic transport protein expression and function have not been investigated in SC rat hepatocytes. (aspetjournals.org)
  • Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. (uni-muenchen.de)
  • New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway. (biomedcentral.com)
  • SLC10A4 belongs to the solute carrier family SLC10 whose founding members are the Na + /taurocholate co-transporting polypeptide (NTCP, SLC10A1 ) and the apical sodium-dependent bile acid transporter (ASBT, SLC10A2 ). (biomedcentral.com)
  • These carriers maintain the enterohepatic circulation of bile acids by sodium-dependent bile acid reabsorption in the gut via ASBT and sodium-dependent bile acid transport into hepatocytes via NTCP [ 2 ]. (biomedcentral.com)
  • Serum metabolomics analysis revealed marked increases in circulating taurocholic acid (TCA) and tauro-beta-muricholic acid (T-b-MCA) in these mice, and forced expression of bile salt export protein by adenovirus in Fxr-null mice ameliorated CCl4-induced liver damage and increases in these serum bile acids. (nih.gov)
  • F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group. (bvsalud.org)
  • When given in high doses, cholic acid replacement therapy has been linked to minor elevations in serum aminotransferase levels, but it has not been linked to instances of clinically apparent acute liver injury with jaundice. (nih.gov)
  • In small, open label trials, cholic acid was found to improve fat soluble vitamin absorption and to ameliorate many of the clinical features of the bile acid synthetic defects including improvement in serum aminotransferase levels, decrease in bilirubin and jaundice and improvement in general health and growth. (nih.gov)
  • In some instances, higher doses of cholic acid were associated with elevations in serum aminotransferase levels. (nih.gov)
  • Affected individuals have a defect involving the excretion of bile salts, which leads to increased serum bile acids. (medscape.com)
  • Reports suggest that troglitazone, and to a lesser extent bosentan, may alter bile acid homeostasis by inhibiting the bile salt export pump. (nih.gov)
  • 16. Troglitazone Inhibits Bile Acid Amidation: A Possible Risk Factor for Liver Injury. (nih.gov)
  • Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation. (uni-muenchen.de)
  • 17. Quantitative profiling of 19 bile acids in rat plasma, liver, bile and different intestinal section contents to investigate bile acid homeostasis and the application of temporal variation of endogenous bile acids. (nih.gov)
  • Farnesoid X receptor (FXR), a ligand-activated transcription factor and a member of the nuclear receptor superfamily, is expressed in intestine and liver where it is activated by bile acid metabolites and controls bile acid homeostasis. (nih.gov)
  • Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis. (biomedcentral.com)
  • Treatment of Fxr-null hepatocytes with TCA, but not T-b-MCA, significantly increased c-Jun-N-terminal kinase (JNK) activation and Ccl2 mRNA, and up-regulation of Ccl2 mRNA was attenuated by co-treatment with the JNK inhibitor SP600125, indicating that TCA directly amplifies hepatocyte inflammatory signaling mainly mediated by JNK in the absence of FXR signaling. (nih.gov)
  • Impact of islatravir on CYP mRNA in human hepatocytes. (bcrablinhibitor.com)
  • 10 μM, 10 min) were employed as measures of canalicular transport protein function in SC rat hepatocytes. (aspetjournals.org)
  • 2, 5] This gene, also known as multidrug resistant protein 3 (MDR3), encodes the transporter for phospholipids across the canalicular membrane of hepatocytes. (medscape.com)
  • 15. Use of sandwich-cultured hepatocytes to evaluate impaired bile acid transport as a mechanism of drug-induced hepatotoxicity. (nih.gov)
  • One hypothesized mechanism for TRO's hepatotoxicity is impairment of bile acid (BA) transport, causing cholestasis and subsequent hepatocellular apoptosis or necrosis. (unc.edu)
  • We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKCa-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. (uni-muenchen.de)
  • It has been shown that one of the most toxic BAs to acinar cells is the secondary BA, taurolithocholic acid (TLC) that forms from LCA after re-absorption from the intestine. (pancreapedia.org)
  • 14. Impaired uptake of conjugated bile acids and hepatitis b virus pres1-binding in na(+) -taurocholate cotransporting polypeptide knockout mice. (nih.gov)
  • Conclusion: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKCa-/PKA-dependent mechanisms. (uni-muenchen.de)
  • Defects in several of the enzymes involved in bile acid synthesis can result in the production of abnormal and insufficient levels of bile acids with resultant fat malabsorption and progressive cholestatic liver disease. (nih.gov)
  • Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. (biomedcentral.com)
  • A single low-dose intraperitoneal injection of carbon tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more severe hepatocyte damage and higher induction of pro-inflammatory mediators, such as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-null mice compared with wild-type mice. (nih.gov)
  • AIM: To investigate the metabolomics of F-G in CCl4 induced acute liver injury in rats and its regulatory effect on the bile acid profile. (bvsalud.org)
  • 1. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes. (nih.gov)
  • 6. Species differences in hepatobiliary disposition of taurocholic acid in human and rat sandwich-cultured hepatocytes: implications for drug-induced liver injury. (nih.gov)
  • In suspended rat hepatocytes, TRO inhibited [3H]TCA uptake more potently than [14C]CDCA uptake. (unc.edu)
  • Recent progress in the past two decades has largely elucidated the molecular mechanisms underlying bile metabolism (including bilirubin, bile acids, cholesterol, phospholipid, and xenobiotics metabolism), hepatocellular transport (including uptake from sinusoidal blood and export to the canaliculus and bile ducts), bile ductular development, the intestinal reabsorption of bile salts, and the regulation of bile acids and cholesterol homeostasis. (biomedcentral.com)
  • in primary hepatocytes. (aspetjournals.org)
  • The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. (bvsalud.org)
  • Cholic (koe' lik) acid is a naturally occurring, primary bile acid that represents a major component of the total bile acid pool in humans. (nih.gov)
  • Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. (biomedcentral.com)
  • Once secreted into the intestine, bile acids help to emulsify fats and aid in their digestion. (nih.gov)
  • Bile acids act in bile to solubilize cholesterol (which is totally insoluble in water) with phospholipids in mixed micelles. (nih.gov)
  • Cholic acid is also a potent signaling molecule and acts as a weak FXR agonist resulting in a decrease in bile acid synthesis and parallel increase in cholesterol. (nih.gov)
  • Bile acids (BAs) are natural end products of cholesterol metabolism (12). (pancreapedia.org)
  • Cholic acid is a naturally occurring bile acid that is used to treat patients with genetic deficiencies in the synthesis of bile acids. (nih.gov)
  • Cholic acid is used therapeutically to treat patients with bile acid synthetic defects due to single enzyme deficiencies. (nih.gov)
  • These studies examined the influence of DEX treatment on transport protein expression and function in sandwich-cultured (SC) rat hepatocytes. (aspetjournals.org)
  • Functional transport studies with different neurotransmitters, bile acids and steroid sulfates were performed in SLC10A4-transfected HEK293 cells, SLC10A4-transfected CAD cells and in Xenopus laevis oocytes. (biomedcentral.com)
  • There have been no reports of clinically apparent liver injury with jaundice attributed to cholic acid therapy given in standard doses. (nih.gov)
  • Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver. (uni-muenchen.de)
  • The mechanism by which high doses of cholic acid might cause liver injury is unclear. (nih.gov)
  • 11. Bile salt export pump inhibitors are associated with bile acid-dependent drug-induced toxicity in sandwich-cultured hepatocytes. (nih.gov)
  • Histopathologically, hepatocellular deterioration along with necrosis, serious depositing involving hemosiderin within Kupffer cellular material along with hepatocytes, bridging fibrosis, as well as therapeutic nodules had been noticed in your hard working liver. (nsc125973inhibitor.com)
  • Cholic acid was given orphan drug approval for use in the United States for treatment of children and adults with bile acid synthetic defects and Zellweger's syndrome (a peroxisomal disorder characterized by progressive liver disease and malabsorption) in 2015. (nih.gov)