4.4 Article

Erythropoietin promotes functional recovery in a mouse model of postoperative ileus

Journal

NEUROGASTROENTEROLOGY AND MOTILITY
Volume 33, Issue 2, Pages -

Publisher

WILEY
DOI: 10.1111/nmo.14049

Keywords

dysmotility; erythropoietin; gastrointestinal tract; intestinal manipulation; intestinal transit time; macrophages; oxidative stress; postoperative ileus

Funding

  1. US Department of Defence [W81XWH-15-PRORP-ARA]
  2. NIH [AR060164-01A]
  3. Clausen Fellowship Grant-University of Rochester [GF455050]
  4. Bradford Fellowship Grant University of Rochester [GF457960]

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This study revealed the beneficial effects of erythropoietin (EPO) in postoperative ileus (POI) by primarily acting through its anti-oxidative and immunomodulatory properties.
Background Dysmotility and postoperative ileus (POI) are major clinical problems after surgical trauma and it is associated with increased intestinal inflammation and oxidative stress. Despite the high occurrence of POI following intra-abdominal surgeries, no effective treatment is currently available. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine with potent anti-inflammatory and anti-oxidative properties, and it is an FDA approved medicine for clinical use. While both EPO and EPO receptors (EPOR) are widely expressed in the gut, the role of EPO in POI is largely unknown. This study was designed to explore the possible beneficial effect of EPO in a mouse model of POI. Methods Mice were subjected to intestinal manipulation to induce standard POI and intestinal transit time was determined at 24-h post-injury with or without EPO treatment (5000 units/kg, once, IP, immediately after intestinal trauma). Intestinal samples were harvested for histological and immunohistochemical analysis. Results Systemic EPO significantly improved intestinal transit time compared with control group and it was associated with significantly increased levels of tissue macrophages and reduced levels of oxidative stress. Conclusions and Inferences This is the first pre-clinical study to document novel beneficial effects of EPO in gut dysmotility and our findings suggest that the beneficial effects of EPO in POI is predominantly mediated by its anti-oxidative and immunomodulatory properties.

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