Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2020; 26(39): 5970-5982
Published online Oct 21, 2020. doi: 10.3748/wjg.v26.i39.5970
Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats
Ana Ferrero-Andrés, Arnau Panisello-Roselló, Joan Roselló-Catafau, Emma Folch-Puy
Ana Ferrero-Andrés, Arnau Panisello-Roselló, Experimental Pathology Department, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas, Barcelona 08036, Catalonia, Spain
Joan Roselló-Catafau, Emma Folch-Puy, Experimental Pathology Department, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona 08036, Catalonia, Spain
Author contributions: Roselló-Catafau J and Folch-Puy E designed the study; Folch-Puy E coordinated the study; Ferrero-Andrés A and Panisello-Roselló A performed the experiments and acquired and analysed data; Ferrero-Andrés A and Folch-Puy E interpreted the data; Ferrero-Andrés A and Folch-Puy E wrote the original draft of the manuscript; Ferrero-Andrés A, Panisello-Roselló A, Roselló-Catafau J and Folch-Puy E reviewed and edited the manuscript; all authors approved the final version of the article.
Supported by the grant from Ministerio de Ciencia e Innovación, No. PID2019-104130RB-I00.
Institutional animal care and use committee statement: All experimental animals’ procedures were conducted in accordance with European Union regulatory standards for animal experimentation (Directive 2010/63/EU on the protection of animals used for scientific purposes). The Ethical Committee for Animal Experimentation (CEEA, ethic approval number: 211/18, University of Barcelona, 11/04/2018) approved the animal experiments.
Conflict-of-interest statement: The authors have disclosed that they do not have any conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Emma Folch-Puy, PhD, Senior Scientist, Experimental Pathology Department, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, C/Roselló 161, Barcelona 08036, Catalonia, Spain. emma.folch@iibb.csic.es
Received: July 21, 2020
Peer-review started: July 21, 2020
First decision: August 8, 2020
Revised: August 12, 2020
Accepted: September 12, 2020
Article in press: September 12, 2020
Published online: October 21, 2020
Processing time: 91 Days and 22.8 Hours
ARTICLE HIGHLIGHTS
Research background

Acute pancreatitis (AP) is a common gastrointestinal condition with an increasing incidence worldwide. The course of the disease ranges from a mild, self-limiting condition to a more severe acute illness with a high morbidity and mortality. Our group has previously demonstrated an anti-inflammatory role for a 35-kDa molecular weight polyethylene glycol (PEG35) in an experimental model of severe necrotizing AP. The therapeutic administration of PEG35 notably alleviated the severity of AP and protected against the associated lung inflammatory response, which is the main contributing factor to early death in patients with this condition.

Research motivation

To date, the treatment of AP continues to be supportive as there are no effective pharmacologic therapies available. Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilic properties combined with a low intrinsic toxicity. In this study, we demonstrated the protective role of PEG35 in a mild form of AP.

Research objectives

To evaluate the effect of PEG35 in experimental models of mild acute pancreatitis in vivo and in vitro.

Research methods

AP was induced by five hourly intraperitoneal injections of cerulein (50 μg/kg/bw). PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α, staurosporine or cerulein. The severity of AP was determined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated cells. Inflammation-induced cell death was also measured in both in vivo and in vitro models of pancreatic damage through apoptosis and necrosis-related assays.

Research results

PEG35 treatment significantly improved pancreatic damage in cerulein-induced AP in rats through reduction on lipase levels and tissue edema. Furthermore, PEG35 ameliorated the inflammatory response and associated cell death in vivo and in vitro, in treated-acinar cells, by lowering inflammatory-related cytokines and iNOS gene expression, levels of apoptotic markers and the activity of lactate dehydrogenase.

Research conclusions

PEG35 ameliorated pancreatic damage in cerulein-induced AP and cultured acinar AR42J-treated cells through the attenuation of the inflammatory response and associated cell death.

Research perspectives

Our study provided evidence of a protective role of PEG35 in a mild form of AP suggesting that PEG35 may be a valuable option in the management of clinical AP.