{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:54:38Z","timestamp":1780484078775,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C32\/18\/035"],"award-info":[{"award-number":["C32\/18\/035"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal ischemia-reperfusion injury (IRI) is a common clinical entity, and its outcome is unpredictable due to the triad of inflammation, increased permeability and bacterial translocation. Polyethylene glycol (PEG) is a polyether compound that is extensively used in pharmacology as an excipient in various products. More recently, this class of products have shown to have potent anti-inflammatory, anti-apoptotic, immunosuppressive and cell-membrane-stabilizing properties. However, its effects on the outcome after intestinal IRI have not yet been investigated. We hypothesized that PEG administration would reduce the effects of intestinal IRI in rodents. In a previously described rat model of severe IRI (45 min of ischemia followed by 60 min of reperfusion), we evaluated the effect of IV PEG administration at different doses (50 and 100 mg\/kg) before and after the onset of ischemia. In comparison to control animals, PEG administration stabilized the endothelial glycocalyx, leading to reduced reperfusion edema, bacterial translocation and inflammatory reaction as well as improved 7-day survival. These effects were seen both in a pretreatment and in a treatment setting. The fact that this product is readily available and safe should encourage further clinical investigations in settings of intestinal IRI, organ preservation and transplantation.<\/jats:p>","DOI":"10.3390\/ijms241310775","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:41:45Z","timestamp":1687999305000},"page":"10775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intravenous Polyethylene Glycol Alleviates Intestinal Ischemia-Reperfusion Injury in a Rodent Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2875-9516","authenticated-orcid":false,"given":"Mathias","family":"Clarysse","sequence":"first","affiliation":[{"name":"Department of Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Abdominal Transplantation Laboratory, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"},{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Accarie","sequence":"additional","affiliation":[{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Panisello-Rosell\u00f3","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques de Barcelona (IIBB), Consejo Superior de Investigaciones Cientificas (CSIC)\u2014Institut D\u2019Investigacions Biom\u00e8dique August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"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":"Translational 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\/0000-0003-4921-466X","authenticated-orcid":false,"given":"Emilio","family":"Canovai","sequence":"additional","affiliation":[{"name":"Department of Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Abdominal Transplantation Laboratory, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"},{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diethard","family":"Monbaliu","sequence":"additional","affiliation":[{"name":"Department of Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Abdominal Transplantation Laboratory, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"},{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"De Hertogh","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory of Translational Cell & Tissue Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Vanuytsel","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of 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":"Department of Abdominal Transplant Surgery & Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Abdominal Transplantation Laboratory, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"},{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals 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":[[2023,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6","article-title":"Pathophysiology of ischaemia-reperfusion injury","volume":"190","author":"Carden","year":"2000","journal-title":"J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13017-022-00443-x","article-title":"Acute mesenteric ischemia: Updated guidelines of the World Society of Emergency Surgery","volume":"17","author":"Bala","year":"2022","journal-title":"World J. Emerg. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2014From mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00423-010-0727-x","article-title":"Intestinal ischemia\/reperfusion: Microcirculatory pathology and functional consequences","volume":"396","author":"Vollmar","year":"2011","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1023\/B:DDAS.0000042232.98927.91","article-title":"Ischemia\u2014Reperfusion Injury of the Intestine and Protective Strategies Against Injury","volume":"49","author":"Mallick","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1002\/jcp.30875","article-title":"AMPK: The key to ischemia-reperfusion injury","volume":"237","author":"Cai","year":"2022","journal-title":"J. Cell. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"854994","DOI":"10.3389\/fphar.2022.854994","article-title":"Mitochondrial DNA Release Contributes to Intestinal Ischemia\/Reperfusion Injury","volume":"13","author":"Liao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/ni.1905","article-title":"Epithelial decision makers: In search of the \u201cepimmunome\u201d","volume":"11","author":"Swamy","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1572-0241.2000.01765.x","article-title":"A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative","volume":"95","author":"DiPalma","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6501","DOI":"10.3748\/wjg.v22.i28.6501","article-title":"Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury","volume":"22","author":"Pasut","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1089\/0897715041651097","article-title":"Polyethylene Glycol Improves Function and Reduces Oxidative Stress in Synaptosomal Preparations following Spinal Cord Injury","volume":"21","author":"Luo","year":"2004","journal-title":"J. Neurotrauma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000209389","article-title":"Polyethylene Glycol Protects Injured Neuronal Mitochondria","volume":"76","author":"Chen","year":"2009","journal-title":"Pathobiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"H1733","DOI":"10.1152\/ajpheart.01054.2010","article-title":"High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function","volume":"300","author":"Malhotra","year":"2011","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.jss.2013.02.035","article-title":"High molecular weight polyethylene glycol (PEG 15-20) maintains mucosal microbial barrier function during intestinal graft preservation","volume":"183","author":"Valuckaite","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jss.2011.10.012","article-title":"Effect of Polyethylene Glycol in Pig Intestinal Allotransplantation Without Immunosuppression","volume":"176","author":"Yandza","year":"2012","journal-title":"J. Surg. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.neulet.2004.02.027","article-title":"Diffusive oxidative stress following acute spinal cord injury in guinea pigs and its inhibition by polyethylene glycol","volume":"359","author":"Luo","year":"2004","journal-title":"Neurosci. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9096549","DOI":"10.1155\/2016\/9096549","article-title":"Polyethylene Glycol Preconditioning: An Effective Strategy to Prevent Liver Ischemia Reperfusion Injury","volume":"2016","author":"Bejaoui","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16203","DOI":"10.3748\/wjg.v20.i43.16203","article-title":"Polyethylene glycol rinse solution: An effective way to prevent ischemia-reperfusion injury","volume":"20","author":"Zaouali","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jtcvs.2014.10.074","article-title":"High-molecular-weight polyethylene glycol inhibits myocardial ischemia\u2013reperfusion injury in vivo","volume":"149","author":"Xu","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"794287","DOI":"10.1155\/2015\/794287","article-title":"Protective Effect of Intravenous High Molecular Weight Polyethylene Glycol on Fatty Liver Preservation","volume":"2015","author":"Bejaoui","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.mvr.2008.11.007","article-title":"Protective effects of high-molecular weight Polyethylene Glycol (PEG) in human lung endothelial cell barrier regulation: Role of actin cytoskeletal rearrangement","volume":"77","author":"Chiang","year":"2009","journal-title":"Microvasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.ajpath.2019.08.019","article-title":"Glycocalyx Degradation in Ischemia-Reperfusion Injury","volume":"190","author":"Abassi","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/TP.0000000000002838","article-title":"Glycocalyx damage within human liver grafts correlates with graft injury and postoperative graft function after orthotopic liver transplantation","volume":"104","author":"Schiefer","year":"2019","journal-title":"Transplantation"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lopez, A., Panisello-Rosello, A., Castro-Benitez, C., and Adam, R. (2018). Glycocalyx Preservation and NO Production in Fatty Livers\u2014The Protective Role of High Molecular Polyethylene Glycol in Cold Ischemia Injury. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082375"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rosello, A.P., da Silva, R.T., Castro, C., Bardallo, R.G., Calvo, M., Folch-Puy, E., Carbonell, T., Palmeira, C., Catafau, J.R., and Adam, R. (2020). Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165703"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ceulemans, L., Verbeke, L., Decuypere, J.-P., Farr\u00e9, R., De Hertogh, G., Lenaerts, K., Jochmans, I., Monbaliu, D., Nevens, F., and Tack, J. (2017). Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169331"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/TA.0000000000000682","article-title":"New low-volume resuscitation solutions containing PEG-20k","volume":"79","author":"Parrish","year":"2015","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1097\/TA.0000000000001155","article-title":"Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock","volume":"81","author":"Plant","year":"2016","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S118","DOI":"10.1097\/01.tp.0000576120.64060.6e","article-title":"First clinical multi-center experience of IGL-1 for intestinal graft preservation","volume":"103","author":"Canovai","year":"2019","journal-title":"Transplantation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/00007890-198804000-00001","article-title":"Principles of solid-organ preservation by cold storage","volume":"45","author":"Belzer","year":"1988","journal-title":"Transplantation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev.med.46.1.235","article-title":"Organ preservation","volume":"46","author":"Southard","year":"1995","journal-title":"Annu. Rev. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0955-470X(05)80025-4","article-title":"The University of Wisconsin organ preservation solution: Components, comparisons, and modifications","volume":"7","author":"Southard","year":"1993","journal-title":"Transpl. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1111\/j.1600-6143.2012.04067.x","article-title":"Intraluminal Polyethylene Glycol Stabilizes Tight Junctions and Improves Intestinal Preservation in the Rat","volume":"12","author":"Oltean","year":"2012","journal-title":"Am. J. Transpl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jss.2014.10.001","article-title":"Luminal solutions protect mucosal barrier during extended preservation","volume":"194","author":"Oltean","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1111\/ajt.16418","article-title":"Luminal polyethylene glycol solution delays the onset of preservation injury in the human intestine","volume":"21","author":"Bagge","year":"2021","journal-title":"Am. J. Transpl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejps.2015.10.020","article-title":"Pharmacokinetics, tissue distribution and excretion of 40kDa PEG and PEGylated rFVIII (N8-GP) in rats","volume":"87","author":"Sternebring","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ferrero-Andr\u00e9s, A., Panisello-Rosell\u00f3, A., Seraf\u00edn, A., Rosell\u00f3-Catafau, J., and Folch-Puy, E. (2020). Polyethylene glycol 35 (PEG35) protects against inflammation in experimental acute necrotizing pancreatitis and associated lung injury. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030917"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cgh.2012.10.027","article-title":"Effects of a Multimodal Management Strategy for Acute Mesenteric Ischemia on Survival and Intestinal Failure","volume":"11","author":"Corcos","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sert, N.P.d., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Clarysse, M., Accarie, A., Farr\u00e9, R., Canovai, E., Monbaliu, D., Gunst, J., De Hertogh, G., Vanuytsel, T., Pirenne, J., and Ceulemans, L.J. (2023). Protective Effect of Oxygen and Isoflurane in Rodent Model of Intestinal Ischemia-Reperfusion Injury. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032587"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/archsurg.1970.01340280030009","article-title":"Intestinal Mucosal Lesion in Low-Flow States: I. A Morphological, Hemodynamic, and Metabolic Reappraisal","volume":"101","author":"Chiu","year":"1970","journal-title":"Arch. Surg."},{"key":"ref_42","first-page":"574","article-title":"The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion","volume":"107","author":"Park","year":"1990","journal-title":"Surgery"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/path.2882","article-title":"Rapid lamina propria retraction and zipper-like constriction of the epithelium preserves the epithelial lining in human small intestine exposed to ischaemia-reperfusion","volume":"224","author":"Grootjans","year":"2011","journal-title":"J. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:02:38Z","timestamp":1760126558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,28]]},"references-count":43,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310775"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310775","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,28]]}}}