{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:26:56Z","timestamp":1788964016552,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Society of Transplantation","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]},{"name":"Flanders Research Foundation (FWO Vlaanderen)","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]},{"name":"Institut George Lopez (IGL)","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]},{"name":"University Hospitals Leuven","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal ischemia is a potentially catastrophic emergency, with a high rate of morbidity and mortality. Currently, no specific pharmacological treatments are available. Previous work demonstrated that pre-treatment with obeticholic acid (OCA) protected against ischemia reperfusion injury (IRI). Recently, a more potent and water-soluble version has been synthesized: Intercept 767 (INT-767). The aim of this study was to investigate if intravenous treatment with INT-767 can improve outcomes after IRI. In a validated rat model of IRI (60 min ischemia + 60 min reperfusion), three groups were investigated (n = 6\/group): (i) sham: surgery without ischemia; (ii) IRI + vehicle; and (iii) IRI + INT-767. The vehicle (0.9% NaCl) or INT-767 (10 mg\/kg) were administered intravenously 15 min after start of ischemia. Endpoints were 7-day survival, serum injury markers (L-lactate and I-FABP), histology (Park\u2013Chiu and villus length), permeability (transepithelial electrical resistance and endotoxin translocation), and cytokine expression. Untreated, IRI was uniformly lethal by provoking severe inflammation and structural damage, leading to translocation and sepsis. INT-767 treatment significantly improved survival by reducing inflammation and preserving intestinal structural integrity. This study demonstrates that treatment with INT-767 15 min after onset of intestinal ischemia significantly decreases IRI and improves survival. The ability to administer INT-767 intravenously greatly enhances its clinical potential.<\/jats:p>","DOI":"10.3390\/ijms241914881","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T07:47:52Z","timestamp":1696405672000},"page":"14881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["INT-767\u2014A Dual Farnesoid-X Receptor (FXR) and Takeda G Protein-Coupled Receptor-5 (TGR5) Agonist Improves Survival in Rats and Attenuates Intestinal Ischemia Reperfusion Injury"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4921-466X","authenticated-orcid":false,"given":"Emilio","family":"Canovai","sequence":"first","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-171X","authenticated-orcid":false,"given":"Ricard","family":"Farr\u00e9","sequence":"additional","affiliation":[{"name":"Translation Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Accarie","sequence":"additional","affiliation":[{"name":"Translation Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9563-7757","authenticated-orcid":false,"given":"Mara","family":"Lauriola","sequence":"additional","affiliation":[{"name":"Translation Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory of Nephrology and Renal Transplantation, Department of Microbiology, Immunology, and Transplantation, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"De Hertogh","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8728-0903","authenticated-orcid":false,"given":"Tim","family":"Vanuytsel","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translation Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"},{"name":"Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8147-8801","authenticated-orcid":false,"given":"Jacques","family":"Pirenne","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4261-7100","authenticated-orcid":false,"given":"Laurens J.","family":"Ceulemans","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Thoracic Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ejvs.2017.01.010","article-title":"Editor\u2019s Choice\u2014Management of the Diseases of Mesenteric Arteries and Veins","volume":"53","author":"Koelemay","year":"2017","journal-title":"Eur. 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