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BioMed Research International
Volume 2013 (2013), Article ID 748160, 10 pages
http://dx.doi.org/10.1155/2013/748160
Research Article

Acetylsalicylic Acid Reduces the Severity of Dextran Sodium Sulfate-Induced Colitis and Increases the Formation of Anti-Inflammatory Lipid Mediators

1Department of Gastroenterology, Hepatology and Endocrinology, Virchow-Hospital, Charité Medical School, Free and Humboldt-University of Berlin, 13353 Berlin, Germany
2Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
3Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4Lurie Family Imaging Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
5Lipidomix GmbH, 13125 Berlin, Germany

Received 18 June 2013; Accepted 19 July 2013

Academic Editor: Gabriella Calviello

Copyright © 2013 Thomas Köhnke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.