Original article Intestinal barrier dysfunction and increased COX-2 gene expression in the gut of elderly rats with acute pancreatitis Denise Frediani Barbeiro a , Marcia Kiyomi Koike a , Ana Maria Mendonça Coelho b , Fabiano Pinheiro da Silva a , Marcel Cerqueira C  esar Machado a, * a Emergency Medicine Department, University of Sao Paulo, Sao Paulo, Brazil b Gastroenterology Department, University of Sao Paulo, Sao Paulo, Brazil article info Article history: Available online xxx Keywords: Pancreatitis Elderly COX-2 Tight junctions Intestine Inflammation abstract Background/Objectives: The clinical course of acute pancreatitis can vary from mild to severe. In its most severe manifestation, acute pancreatitis is associated with an exacerbated systemic inflammatory response and high mortality rates. The severe form of acute pancreatitis is more frequent in elderly patients than in young patients, but the mechanisms underlying this difference are still under investigation. Methods: Rats were divided into two groups as follows: Group 1, young rats; and Group 2, old rats. Acute pancreatitis group was induced by a retrograde injection of a sodium taurocholate solution into the biliopancreatic duct. Using this model of acute pancreatic injury, we designed a study to investigate possible differences in microbial translocation and characteristics of the intestinal barrier between elderly and young rats. Results: There was a significantly higher number of bacterial colonies in the pancreas of elderly rats compared with young rats following pancreas injury, which was associated with a more severe local intestinal inflammatory response that included elevated gene expression of COX-2 and a decreased gene expression of tight junction proteins. Conclusions: We conclude that intestinal damage during acute pancreatitis is exacerbated in elderly rats compared with young rats and that COX-2 inhibition could be a potential therapeutic target to offer tailored treatment for acute pancreatitis in the elderly. Copyright © 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Introduction Acute pancreatitis (AP) in elderly patients is characterized by increased morbidity, higher mortality, and a significant financial impact compared with young patients, despite the fact that the local complications are similar and there are no substantial differ- ences in systemic responses [1e3]. The mechanisms underlying this observation have been extensively investigated but remain unknown. Possible explanations include a reduced immune- inflammatory response to injury, the presence of co-morbidities [2], defective pancreatic protective mechanisms [4], or increased intestinal damage associated with more severe bacterial trans- location in the elderly, a concept that was supported by a previous study suggesting higher systemic damage occurs in the older population [5]. Indeed, dysfunction of the intestinal barrier and the resulting bacterial translocation from the intestinal lumen to distant organs [6] has been implicated as the main culprit in the pathophysiology of infected severe AP [7,8]. Because intestinal inflammation promotes increased bacterial translocation during AP [9], we postulated that the basal pro- inflammatory status typical in elderly individuals [10], also known as “inflammaging”, facilitates intestinal injury during AP and promotes increased bacterial translocation, a more deleterious systemic inflammation [11], and distant organ damage. The aim of the present study was to investigate the intestinal barrier in elderly and young rats as well as the mechanisms responsible for microbial Abbreviations: AP, acute pancreatitis; COX-2, cyclooxygenase-2; TNFa, tumor necrosis factor alpha; IL-10, interleukin-10; JAM-A, junctional adhesion molecule A; ZO-1, zona occludens protein 1. * Corresponding author. Faculdade de Medicina da Universidade de S~ ao Paulo, Laborat orio de Emerg^ encias Clínicas (LIM-51), Av. Dr. Arnaldo, 455 sala 3189, CEP 01246-000, S~ ao Paulo e SP, Brazil. Tel./fax: þ55 11 3061 8480. E-mail address: mccm37@uol.com.br (M.C. C esar Machado). Contents lists available at ScienceDirect Pancreatology journal homepage: www.elsevier.com/locate/pan http://dx.doi.org/10.1016/j.pan.2015.10.012 1424-3903/Copyright © 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Pancreatology xxx (2015) 1e5 Please cite this article in press as: Barbeiro DF, et al., Intestinal barrier dysfunction and increased COX-2 gene expression in the gut of elderly rats with acute pancreatitis, Pancreatology (2015), http://dx.doi.org/10.1016/j.pan.2015.10.012