%0 Journal Article
%T Anti-Fibrotic Potential of All Trans Retinoic Acid in Inflammatory Bowel Disease
%A Dominick L Auci
%A Gerald W Dryden
%A Nejat K Egilmez
%J International Journal of Pancreatology | Journal of Gastroenterology and Liver Diseases
%D 2018
%R 10.15226/2374-815X/6/3/001126
%X Inflammatory bowel disease (IBD) embraces Crohn¡¯s disease (CD), ulcerative colitis (UC) and the less common indeterminate colitis, all chronic inflammatory processes of the gastrointestinal (GI) tract. Together, they cause significant morbidity for a million and a half Americans [1]. Symptoms include diarrhea, nausea, abdominal pain, weight loss, which can occasionally prove fatal (i.e., toxic megacolon, perforated bowel) [2]. Patients are also at increased risk for colorectal cancer [3]. First line treatments, including various anti-inflammatory agents and antibiotics, are variably effective against active disease [4]. Remissions can be short-lived and uncontrolled activity is associated with significant side-effects [3]. Gut fibrosis will require most patients (80% and 45% of CD and UC patients, respectively) to undergo surgery [4]. Over the last decade, the so-called biological response modifiers or ¡®biologics¡¯, macromolecules that target inflammatory lymphocytes or the cytokines they produce, have emerged as effective therapeutic agents [5]. For example, infliximab, a chimeric anti-human tumor necrosis factor (TNF)-¦Á antibody earned FDA approval almost 20 years ago, based on a high response rate, significant mucosal and fistula healing and long-term remissions in both CD and UC. Additional targets of biologics, either marketed or in various stages of development, include anti-p40, anti-p19, anti-interleukin (IL)-12/23, and antialpha 4/beta 7 integrin antibodies [5, 6]. However, an estimated 30% of patients will not respond to such treatments, and of those who initially respond, 50% will relapse within a year risking significant, often serious side effects including infections and increased risk of cancer. So far, biologics have had only a modest impact on surgery rates [7]. The need for novel therapies remains acute. Literature reports indicate that All trans retinoic acid (ATRA) provides benefit in various rodent models of IBD, including potential anti-fibrotic activity [8, 9]. Retinoic acid can exist in the body as any of five different chemical isomers (all-trans- RA, 9-cisRA, 13-cisRA, 11-cisRA and 9, 13-dicisRA). ATRA is the biologically active isomer and the primary enzymatic product of retinaldehyde oxidation. The retinoic acid family regulates a wide range of biological processes, including embryonic development, reproduction, vision, cell growth and differentiation, as well as, apoptosis and inflammation [10]. Topical ATRA is known as tretinoin, and is currently marketed under several trade names such as Retin-A£¿, Retin-A Micro£¿, Atralin£¿,
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