{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:04:54Z","timestamp":1780452294083,"version":"3.54.1"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute pancreatitis is an inflammatory disorder of the pancreas. Its presentation ranges from self-limiting disease to acute necrotizing pancreatitis (ANP) with multiorgan failure and a high mortality. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic, and water-soluble chemicals composed of repeating units of ethylene glycol. The present article explores the effect of PEG35 administration on reducing the severity of ANP and associated lung injury. ANP was induced by injection of 5% sodium taurocholate into the biliopancreatic duct. PEG35 was administered intravenously either prophylactically or therapeutically. Three hours after ANP induction, pancreas and lung tissue samples and blood were collected and ANP severity was assessed. To evaluate the inflammatory response, gene expression of pro-inflammatory cytokines and chemokine and the changes in the presence of myeloperoxidase and adhesion molecule levels were determined in both the pancreas and the lung. To evaluate cell death, lactate dehydrogenase (LDH) activity and apoptotic cleaved caspase-3 localization were determined in plasma and in both the pancreatic and lung tissue respectively. ANP-associated local and systemic inflammatory processes were reduced when PEG35 was administered prophylactically. PEG35 pre-treatment also protected against acute pancreatitis-associated cell death. Notably, the therapeutic administration of PEG35 significantly decreased associated lung injury, even when the pancreatic lesion was equivalent to that in the untreated ANP-induced group. Our results support a protective role of PEG35 against the ANP-associated inflammatory process and identify PEG35 as a promising tool for the treatment of the potentially lethal complications of the disease.<\/jats:p>","DOI":"10.3390\/ijms21030917","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T05:55:46Z","timestamp":1580450146000},"page":"917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Polyethylene Glycol 35 (PEG35) Protects against Inflammation in Experimental Acute Necrotizing Pancreatitis and Associated Lung Injury"],"prefix":"10.3390","volume":"21","author":[{"given":"Ana","family":"Ferrero-Andr\u00e9s","sequence":"first","affiliation":[{"name":"Experimental Pathology Department, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), Barcelona, 08036 Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnau","family":"Panisello-Rosell\u00f3","sequence":"additional","affiliation":[{"name":"Experimental Pathology Department, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), Barcelona, 08036 Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Seraf\u00edn","sequence":"additional","affiliation":[{"name":"PCB Animal Facility-Parc Cient\u00edfic de Barcelona, Barcelona, 08028 Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Rosell\u00f3-Catafau","sequence":"additional","affiliation":[{"name":"Experimental Pathology Department, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, 08036 Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6277-9027","authenticated-orcid":false,"given":"Emma","family":"Folch-Puy","sequence":"additional","affiliation":[{"name":"Experimental Pathology Department, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, 08036 Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0140-6736(14)60649-8","article-title":"Acute pancreatitis","volume":"386","author":"Lankisch","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1136\/gutjnl-2012-302779","article-title":"Acute Pancreatitis Classification Working G: Classification of acute pancreatitis\u20142012: Revision of the Atlanta classification and definitions by international consensus","volume":"62","author":"Banks","year":"2013","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.rmed.2012.06.003","article-title":"Acute lung injury in acute pancreatitis\u2014Awaiting the big leap","volume":"106","author":"Akbarshahi","year":"2012","journal-title":"Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.xphs.2015.11.015","article-title":"PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs","volume":"105","author":"Turecek","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1177\/0192623315591171","article-title":"PEGylated Biopharmaceuticals: Current Experience and Considerations for Nonclinical Development","volume":"43","author":"Ivens","year":"2015","journal-title":"Toxicol. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6288","DOI":"10.1002\/anie.200902672","article-title":"Poly(ethylene glycol) in drug delivery: Pros and cons as well as potential alternatives","volume":"49","author":"Knop","year":"2010","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_7","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_8","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_9","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. Heart Circ. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/CCM.0b013e3181c8fcd0","article-title":"Low-molecular-weight polyethylene glycol improves survival in experimental sepsis","volume":"38","author":"Ackland","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00384-006-0232-4","article-title":"Polyethylene glycol enhances colonic barrier function and ameliorates experimental colitis in rats","volume":"22","author":"Videla","year":"2007","journal-title":"Int. J. Colorectal. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0002-9610(98)00102-0","article-title":"Polyethylene glycol 4000 attenuates adhesion formation in rats by suppression of peritoneal inflammation and collagen incorporation","volume":"176","author":"Nagelschmidt","year":"1998","journal-title":"Am. J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.canlet.2004.10.029","article-title":"Polyethylene glycol reduces inflammation and aberrant crypt foci in carcinogen-initiated rats","volume":"223","author":"Karlsson","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_14","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_15","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_16","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.pan.2018.05.002","article-title":"Interleukin-6 significantly improves predictive value of systemic inflammatory response syndrome for predicting severe acute pancreatitis","volume":"18","author":"Jain","year":"2018","journal-title":"Pancreatology"},{"key":"ref_17","first-page":"349","article-title":"SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors","volume":"57","author":"Gregoric","year":"2010","journal-title":"Hepatogastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.3389\/fimmu.2018.02712","article-title":"Role of Platelets in Leukocyte Recruitment and Resolution of Inflammation","volume":"9","author":"Rossaint","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00535-018-1500-0","article-title":"Adhesion molecules and pancreatitis","volume":"54","author":"Sato","year":"2019","journal-title":"J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/SHK.0000000000000211","article-title":"Delayed Neutralization of IL-6 Reduces Organ Injury, Selectively Suppresses Inflammatory Mediator and Partially Normalizes Immune Dysfunction following Trauma and Hemorrhagic Shock","volume":"42","author":"Yong","year":"2014","journal-title":"Shock"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.pan.2017.05.392","article-title":"IL-6 and CRP are superior in early differentiation between mild and non-mild acute pancreatitis","volume":"17","author":"Sternby","year":"2017","journal-title":"Pancreatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4103\/ijccm.IJCCM_478_16","article-title":"Interleukin-6: An Early Predictive Marker for Severity of Acute Pancreatitis","volume":"21","author":"Rao","year":"2017","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1517\/14728222.2010.504717","article-title":"Targeting P-selectin in acute pancreatitis","volume":"14","author":"Hackert","year":"2010","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_24","first-page":"8","article-title":"Icam-1 and acute pancreatitis complicated by acute lung injury","volume":"10","author":"Zhang","year":"2009","journal-title":"JOP"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainres.2007.03.091","article-title":"Polyethylene glycol inhibits apoptotic cell death following traumatic spinal cord injury","volume":"1155","author":"Luo","year":"2007","journal-title":"Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1111\/j.1600-6143.2006.01343.x","article-title":"Protective effect of PEG 35,000 Da on renal cells: Paradoxical activation of JNK signaling pathway during cold storage","volume":"6","author":"Dutheil","year":"2006","journal-title":"Am. J. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1136\/gut.2007.127472","article-title":"Oxidised lipids present in ascitic fluid interfere with the regulation of the macrophages during acute pancreatitis, promoting an exacerbation of the inflammatory response","volume":"57","author":"Gutierrez","year":"2008","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gks596","article-title":"Primer3\u2014New capabilities and interfaces","volume":"40","author":"Untergasser","year":"2012","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:18Z","timestamp":1760172798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,30]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21030917"],"URL":"https:\/\/doi.org\/10.3390\/ijms21030917","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,30]]}}}