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Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis

Acute pancreatitis (AP) is a major, globally increasing gastrointestinal disease and a biliary origin is the most common cause. However, the effects of bile acids (BAs), given systemically, on the pancreas and on disease severity remains elusive. In this study, we have investigated the roles of diff...

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Autores principales: Tran, Quang Trung, Sendler, Matthias, Wiese, Mats L., Doller, Julia, Zierke, Lukas, Gischke, Marcel, Glaubitz, Juliane, Tran, Van Huy, Lalk, Michael, Bornscheuer, Uwe T., Weiss, Frank Ulrich, Lerch, Markus M., Aghdassi, Ali A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655547/
https://www.ncbi.nlm.nih.gov/pubmed/36362379
http://dx.doi.org/10.3390/ijms232113592
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author Tran, Quang Trung
Sendler, Matthias
Wiese, Mats L.
Doller, Julia
Zierke, Lukas
Gischke, Marcel
Glaubitz, Juliane
Tran, Van Huy
Lalk, Michael
Bornscheuer, Uwe T.
Weiss, Frank Ulrich
Lerch, Markus M.
Aghdassi, Ali A.
author_facet Tran, Quang Trung
Sendler, Matthias
Wiese, Mats L.
Doller, Julia
Zierke, Lukas
Gischke, Marcel
Glaubitz, Juliane
Tran, Van Huy
Lalk, Michael
Bornscheuer, Uwe T.
Weiss, Frank Ulrich
Lerch, Markus M.
Aghdassi, Ali A.
author_sort Tran, Quang Trung
collection PubMed
description Acute pancreatitis (AP) is a major, globally increasing gastrointestinal disease and a biliary origin is the most common cause. However, the effects of bile acids (BAs), given systemically, on the pancreas and on disease severity remains elusive. In this study, we have investigated the roles of different circulating BAs in animal models for AP to elucidate their impact on disease severity and the underlying pathomechanisms. BAs were incubated on isolated acini and AP was induced through repetitive injections of caerulein or L-arginine; pancreatic duct ligation (PDL); or combined biliopancreatic duct ligation (BPDL). Disease severity was assessed using biochemical and histological parameters. Serum cholecystokinin (CCK) concentrations were determined via enzyme immunoassay. The binding of the CCK1 receptor was measured using fluorescence-labeled CCK. In isolated acini, hydrophobic BAs mitigated the damaging effects of CCK. The same BAs further enhanced pancreatitis in L-arginine- and PDL-based pancreatitis, whereas they ameliorated pancreatic damage in the caerulein and BPDL models. Mechanistically, the binding affinity of the CCK1 receptor was significantly reduced by hydrophobic BAs. The hydrophobicity of BAs and the involvement of CCK seem to be relevant in the course of AP. Systemic BAs may affect the severity of AP by interfering with the CCK1 receptor.
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spelling pubmed-96555472022-11-15 Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis Tran, Quang Trung Sendler, Matthias Wiese, Mats L. Doller, Julia Zierke, Lukas Gischke, Marcel Glaubitz, Juliane Tran, Van Huy Lalk, Michael Bornscheuer, Uwe T. Weiss, Frank Ulrich Lerch, Markus M. Aghdassi, Ali A. Int J Mol Sci Article Acute pancreatitis (AP) is a major, globally increasing gastrointestinal disease and a biliary origin is the most common cause. However, the effects of bile acids (BAs), given systemically, on the pancreas and on disease severity remains elusive. In this study, we have investigated the roles of different circulating BAs in animal models for AP to elucidate their impact on disease severity and the underlying pathomechanisms. BAs were incubated on isolated acini and AP was induced through repetitive injections of caerulein or L-arginine; pancreatic duct ligation (PDL); or combined biliopancreatic duct ligation (BPDL). Disease severity was assessed using biochemical and histological parameters. Serum cholecystokinin (CCK) concentrations were determined via enzyme immunoassay. The binding of the CCK1 receptor was measured using fluorescence-labeled CCK. In isolated acini, hydrophobic BAs mitigated the damaging effects of CCK. The same BAs further enhanced pancreatitis in L-arginine- and PDL-based pancreatitis, whereas they ameliorated pancreatic damage in the caerulein and BPDL models. Mechanistically, the binding affinity of the CCK1 receptor was significantly reduced by hydrophobic BAs. The hydrophobicity of BAs and the involvement of CCK seem to be relevant in the course of AP. Systemic BAs may affect the severity of AP by interfering with the CCK1 receptor. MDPI 2022-11-05 /pmc/articles/PMC9655547/ /pubmed/36362379 http://dx.doi.org/10.3390/ijms232113592 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tran, Quang Trung
Sendler, Matthias
Wiese, Mats L.
Doller, Julia
Zierke, Lukas
Gischke, Marcel
Glaubitz, Juliane
Tran, Van Huy
Lalk, Michael
Bornscheuer, Uwe T.
Weiss, Frank Ulrich
Lerch, Markus M.
Aghdassi, Ali A.
Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
title Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
title_full Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
title_fullStr Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
title_full_unstemmed Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
title_short Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
title_sort systemic bile acids affect the severity of acute pancreatitis in mice depending on their hydrophobicity and the disease pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9655547/
https://www.ncbi.nlm.nih.gov/pubmed/36362379
http://dx.doi.org/10.3390/ijms232113592
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