scholarly journals Glyceric Prodrug of Ursodeoxycholic Acid (UDCA): Novozym 435-Catalyzed Synthesis of UDCA-Monoglyceride

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5966
Author(s):  
Federico Zappaterra ◽  
Stefania Costa ◽  
Daniela Summa ◽  
Bruno Semeraro ◽  
Virginia Cristofori ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Immobilized Lipase ◽  
Critical Role ◽  
Clinical Effectiveness ◽  
Water Soluble ◽  
Novozym 435 ◽  
Biliary Cirrhosis ◽  
Enzymatic Esterification

Bile acids (BAs) are a family of steroids synthesized from cholesterol in the liver. Among bile acids, ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones. The clinical effectiveness of UDCA includes its choleretic activity, the capability to inhibit hydrophobic bile acid absorption by the intestine under cholestatic conditions, reducing cholangiocyte injury, stimulation of impaired biliary output, and inhibition of hepatocyte apoptosis. Despite its clinical effectiveness, UDCA is poorly soluble in the gastro-duodeno-jejunal contents, and pharmacological doses of UDCA are not readily soluble in the stomach and intestine, resulting in incomplete absorption. Indeed, the solubility of 20 mg/L greatly limits the bioavailability of UDCA. Since the bioavailability of drug products plays a critical role in the design of oral administration dosages, we investigated the enzymatic esterification of UDCA as a strategy of hydrophilization. Therefore, we decided to enzymatically synthesize a glyceric ester of UDCA bile acid to produce a more water-soluble molecule. The esterification reactions between UDCA and glycerol were performed with an immobilized lipase B from Candida antarctica (Novozym 435) in solvent-free and solvent-assisted systems. The characterization of the UDCA-monoglyceride, enzymatically synthesized, has been performed by 1H-NMR, 13C-NMR, COSY, HSQC, HMBC, IR, and MS spectroscopy.

scholarly journals Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11−/− mouse: transport and gene expression studies

2013 ◽  
Vol 305 (4) ◽  
pp. G286-G294 ◽  
Author(s):  
Renxue Wang ◽  
Lin Liu ◽  
Jonathan A. Sheps ◽  
Dana Forrest ◽  
Alan F. Hofmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Cirrhosis ◽  
Beneficial Effects ◽  
Elevated Liver Enzymes ◽  
Genes Encoding ◽  
End Stage

The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice ( abcb11 −/−) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11−/− mice. Feeding UDCA to abcb11−/− mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11−/− mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11−/− mice. UDCA fed to abcb11−/− mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11−/− mice.

Hepatic bile acid handling in primary biliary cirrhosis: Effect of ursodeoxycholic acid

2000 ◽  
Vol 118 (4) ◽  
pp. A901
Author(s):  
Paolo Pazzi ◽  
Raffaella Scagliarini ◽  
Susanna Gamberini ◽  
Napoleone Prandini ◽  
Sergio Gullini ◽  
...  
Keyword(s):  
Bile Acid ◽  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Biliary Cirrhosis ◽  
Hepatic Bile

Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis

1993 ◽  
Vol 38 (5) ◽  
pp. 896-902 ◽  
Author(s):  
Giuseppe Mazzella ◽  
Paolo Parini ◽  
Franco Bazzoli ◽  
Nicola Villanova ◽  
Davide Festi ◽  
...  
Keyword(s):  
Bile Acid ◽  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Biliary Cirrhosis ◽  
Early Stages ◽  
Acid Administration

Ursodeoxycholic acid induces significant changes of plasma bile acids in primary biliary cirrhosis

1989 ◽  
Vol 9 ◽  
pp. S231
Author(s):  
A Stiehl ◽  
R Raedsch ◽  
B Möller ◽  
U Hopf ◽  
E Lotterer ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Biliary Cirrhosis

scholarly journals Overview of Bile Acids Signaling and Perspective on the Signal of Ursodeoxycholic Acid, the Most Hydrophilic Bile Acid, in the Heart

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 159 ◽  
Author(s):  
Noorul Izzati Hanafi ◽  
Anis Syamimi Mohamed ◽  
Siti Hamimah Sheikh Abdul Kadir ◽  
Mohd Hafiz Dzarfan Othman
Keyword(s):  
Heart Failure ◽  
Bile Acid ◽  
Chronic Heart Failure ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
G Protein ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptors ◽  
Heart Failure Patients ◽  
G Protein Coupled

Bile acids (BA) are classically known as an important agent in lipid absorption and cholesterol metabolism. Nowadays, their role in glucose regulation and energy homeostasis are widely reported. BAs are involved in various cellular signaling pathways, such as protein kinase cascades, cyclic AMP (cAMP) synthesis, and calcium mobilization. They are ligands for several nuclear hormone receptors, including farnesoid X-receptor (FXR). Recently, BAs have been shown to bind to muscarinic receptor and Takeda G-protein-coupled receptor 5 (TGR5), both G-protein-coupled receptor (GPCR), independent of the nuclear hormone receptors. Moreover, BA signals have also been elucidated in other nonclassical BA pathways, such as sphingosine-1-posphate and BK (large conductance calcium- and voltage activated potassium) channels. Hydrophobic BAs have been proven to affect heart rate and its contraction. Elevated BAs are associated with arrhythmias in adults and fetal heart, and altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile, in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase in serum bile acid concentrations. In contrast, the most hydrophilic BA, known as ursodeoxycholic acid (UDCA), has been found to be beneficial in improving peripheral blood flow in chronic heart failure patients and in protecting the heart against reperfusion injury. This review provides an overview of BA signaling, with the main emphasis on past and present perspectives on UDCA signals in the heart.

Ursodeoxycholic acid–induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis

Hepatology ◽  
1990 ◽  
Vol 12 (3) ◽  
pp. 492-497 ◽  
Author(s):  
Adolf Stiehl ◽  
Gerda Rudolph ◽  
Richard Raedsch ◽  
Bernd Moller ◽  
Ulrich Hopf ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Biliary Cirrhosis ◽  
Induced Changes

Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis

Hepatology ◽  
1989 ◽  
Vol 10 (4) ◽  
pp. 414-419 ◽  
Author(s):  
Ashok K. Batta ◽  
Gerald Salen ◽  
Renu Arora ◽  
Sarah Shefer ◽  
G. Stephen Tint ◽  
...  
Keyword(s):  
Bile Acid ◽  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Biliary Cirrhosis

scholarly journals Urisodeoxycholic Acid in Treatment of Liver Cirrhosis

2021 ◽  
Vol 9 (9) ◽  
pp. 1869-1873
Author(s):  
Sangale Mukta
Keyword(s):  
Liver Cirrhosis ◽  
Bile Acid ◽  
Primary Biliary Cirrhosis ◽  
Ursodeoxycholic Acid ◽  
Primary Sclerosing Cholangitis ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Biliary Cirrhosis ◽  
Chronic Liver Diseases

Abstract: Ursodeoxycholic acid is a dihy- droxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholer- esis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established.Ursodeoxycholic acid prolongs survival in primary biliary cirrhosis and it improves biochemical parameters of cholestasis in various other cholestatic disorders including primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis and total parenteral nutritioninduced cholestasis. However, a positive effect on survival remains to be established in these diseases. Ursodeoxycholic acid is of unproven efficacy in non- cholestatic disorders such as acute rejection after liver transplantation, non-alcoholic steatohepatitis, alcoholic liver disease and chronic viral hepatitis. This review outlines the present knowledge of the Pharmacology of ursodeoxycholic acid, and presents data from clinical trials on its use in chronic liver diseases. Keywords: Liver cirrhosis, Urisodeoxycholic acid

Sign in / Sign up

Export Citation Format

Share Document