Efficacy and safety of erythropoietin in a chronic model of Inflammatory Bowel Disease

• Published in: Biomedicine & pharmacotherapy Vol. 156; p. 113944
• Main Authors: Silva, Inês, Estarreja, João, Pinto, Rui, Mateus, Vanessa
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.12.2022; Elsevier
• Subjects: Anti-inflammatory effect; Drug repositioning; Erythropoietin; Experimental colitis; Inflammatory bowel disease; TNBS-induced colitis; Inflammatory bowel disease; Drug repositioning; Experimental colitis; Anti-inflammatory effect; Erythropoietin; TNBS-induced colitis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113944

Inflammatory Bowel Disease (IBD) is recognized as a group of chronic inflammatory disorders, localized in the gastrointestinal tract, which does not have a cure known. Indeed, the pharmacological approaches, commonly used, demonstrate significant toxicity, which highlights the need of investigating new possible treatments. Erythropoietin (EPO) is clinically used in anemic patients, with chronic renal insufficiency, due to its erythropoietic effect. However, it has also been described other non-erythropoietic effects, such as an anti-inflammatory role. There is already preclinical evidence about its anti-inflammatory effect in the IBD context, namely in an acute model of colitis in mice. Therefore, it is relevant to ascertain its anti-inflammatory effect in a chronic model, but mainly its hematopoietic side effect, during chronic treatment. Aim: This experiment aims to evaluate the efficacy and safety of EPO treatment in a chronic 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rodents. Methods: The induction of chronic colitis consistedofn five weekly intrarectal administrations of 1% TNBS, and then mice were treated daily with 500 IU/Kg or 1000 IU/Kg of EPO, through intraperitoneal injections, for 14 days. Results: EPO demonstrated a significant anti-inflammatory effect, translated by a significant reduction of the concentration oftumorr necrosis factor-α, fecal calprotectin, and fecal hemoglobin. Moreover, it has also been demonstrated to be safe, considering the cardiovascular system, in terms of extraintestinal manifestations, namely at renal and hepatic functions. Conclusions: EPO demonstrated to be a promising pharmacological approach to be considered in the management of IBD, being an interesting target for drug repositioning. [Display omitted] •Erythropoietin has erythropoietic and non-erythropoietic effects.•Animal models have demonstrated the anti-inflammatory potential of erythropoietin.•Erythropoietin has decreased TNF-α, fecal calprotectin, and fecal hemoglobin.•Erythropoietin demonstrated to be safe considering cardiovascular system.•Erythropoietin demonstrated to be a promising pharmacological approach in IBD.