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      Five-Aminosalicylic Acid: An Update for the Reappraisal of an Old Drug

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          Abstract

          Inflammatory bowel disease (IBD) comprises several conditions with chronic or recurring immune response and inflammation of the gastrointestinal apparatus, of which ulcerative colitis and Crohn's disease are the commonest forms. This disease has a significant prevalence and it is of an unknown aethiology. Five-aminosalicylic acid (5-ASA) and its derivatives are among the oldest drugs approved for the treatment of the IBD. In this review we reapprise aspects of 5-ASA mechanism of action, safety, and efficacy that in our opinion make it a valuable drug that can be fruitfully tailored in personalised treatments as a therapeutic option alongside other immune-modifying agents.

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          Myocarditis: current trends in diagnosis and treatment.

          G Dec, Jared W. Magnani (2006)
          Article 0 comments Cited 130 times – based on 0 reviews     Review now
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            Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ

            Christel Rousseaux, Bruno Lefebvre, Laurent Dubuquoy … (2005)
            5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator–activated receptor-γ (PPAR-γ) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-γ+/− mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-γ expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element–driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-γ as a target of 5-ASA underlying antiinflammatory effects in the colon.
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              Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies.

              J. Walsh, Jonathan Terdiman, Fernando Velayos (2005)
              We performed a systematic review with metaanalysis of observational studies evaluating the association between 5-ASA use and colorectal cancer (CRC) or dysplasia among patients with ulcerative colitis. We conducted a search of Medline Embase Biosis, Web of Science, Cochrane Collaboration, manually reviewed the literature, and consulted with experts. Studies were included if they 1) evaluated and clearly defined exposure to 5-aminosalicylates in patients with ulcerative colitis, 2) reported CRC or dysplasia outcomes, 3) reported relative risks or odds ratio or provided data for their calculations. Quantitative analysis using a random-effects model is presented. Nine studies (3 cohort, 6 case-control) containing 334 cases of CRC, 140 cases of dysplasia, and a total of 1,932 subjects satisfied all inclusion criteria. Five studies reported CRC outcomes alone, two studies reported separate cancer and dysplasia outcomes, and two studies reported a combined outcome of CRC or dysplasia. All primary estimates are homogenous. Pooled analysis showed a protective association between use of 5-aminosalicylates and CRC (OR=0.51; 95% confidence interval (CI): 0.37-0.69) or a combined endpoint of CRC/dysplasia (OR 0.51; 95% CI: 0.38-0.69). 5-ASA use was not associated with a lower risk of dysplasia, although only two studies evaluated this outcome (OR=1.18; 95% CI: 0.41-3.43). Pooled results of observational studies support a protective association between 5-aminosalicylates and CRC or a combined endpoint of CRC/dysplasia in patients with ulcerative colitis. Additional studies analyzing the effect of 5-ASA on risk of dysplasia are needed.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Gastroenterol Res Pract
                Journal ID (iso-abbrev): Gastroenterol Res Pract
                Journal ID (publisher-id): GRP
                Title: Gastroenterology Research and Practice
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-6121
                ISSN (Electronic): 1687-630X
                Publication date (Print): 2015
                Publication date (Electronic): 21 January 2015
                Volume: 2015
                Electronic Location Identifier: 456895
                Affiliations
                1Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, Italy
                2Unit of General Surgery, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University Hospital “Luigi Sacco”, Università di Milano, 20157 Milan, Italy
                3Department for Innovation in Biological, Agro-Food and Forest Systems, Università della Tuscia, 01100 Viterbo, Italy
                4Scientific Institute, IRCCS Eugenio Medea, 23842 Bosisio Parini, Italy
                Author notes
                *Piergiorgio Danelli: piergiorgio.danelli@ 123456unimi.it and

                Academic Editor: Bjørn Moum

                Article
                DOI: 10.1155/2015/456895
                PMC ID: 4320793
                PubMed ID: 25685145
                SO-VID: 2b2c5b7e-0612-4aae-946f-c7f7cf91baa6
                Copyright © Copyright © 2015 Cristiana Perrotta et al.
                License:

                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.

                History
                Date received : 10 November 2014
                Date accepted : 29 December 2014
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Gastroenterology & Hepatology
                Data availability:
                ScienceOpen disciplines: Gastroenterology & Hepatology

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