Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia
| Autor: | Dicky Struik, Rick Havinga, Lori W E van der Schoor, Sanne de Wit, Johan W. Jonker, Robert H. Tukey, Libor Vítek, Andrea B. Schreuder, Henkjan J. Verkade, Anna Bertolini, Petra Valášková, Elvira Mennillo, André A. Weber, Shujuan Chen, Jana Jašprová, Vincent W. Bloks, Eva Rettenmeier |
|---|---|
| Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cytoplasmic and Nuclear medicine.medical_treatment Rats Gunn Exchange transfusion Receptors Cytoplasmic and Nuclear Pharmacology OBETICHOLIC ACID chemistry.chemical_compound Mice 0302 clinical medicine Neonatal Receptors Gastrointestinal models Hyperbilirubinemia Pediatric Pregnane X receptor Multidisciplinary Gunn Liver Disease Ursodeoxycholic Acid Obeticholic acid MOUSE MODEL Jaundice INTESTINAL MICROFLORA Ursodeoxycholic acid Treatment Outcome Liver BILIRUBIN 030220 oncology & carcinogenesis Medicine Patient Safety medicine.symptom Hyperbilirubinemia Neonatal medicine.drug Agonist EXPRESSION Bilirubin medicine.drug_class BIRTH Science Chronic Liver Disease and Cirrhosis Paediatric research Chenodeoxycholic Acid Article Bile Acids and Salts 03 medical and health sciences Ileum medicine MANAGEMENT Animals UDP-GLUCURONOSYLTRANSFERASE ACTIVITY PHOTOTHERAPY business.industry Prevention Neurosciences Isoxazoles Perinatal Period - Conditions Originating in Perinatal Period medicine.disease Rats 030104 developmental biology chemistry Kernicterus PREGNANE-X-RECEPTOR business Digestive Diseases |
| Zdroj: | Scientific Reports, 11(1):11107. Nature Publishing Group Scientific Reports Scientific reports, vol 11, iss 1 Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Neonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10–14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink