@article{8644823,
  abstract     = {{Background Postoperative ileus (POI), the impairment of gastrointestinal motility after abdominal surgery, is mainly due to intestinal muscular inflammation. Carbon monoxide (CO)-releasing compounds were shown to exert an anti-inflammatory effect in murine POI partially through induction of heme oxygenase-1 (HO-1). The influence of hemin and dimethyl fumarate (DMF), currently used for multiple sclerosis (MS), was therefore tested in murine POI.

Methods C57BL/6J mice were anesthetized and after laparotomy, POI was induced via intestinal manipulation (IM). Animals were treated with either 30 mg kg(-1) hemin intraperitoneally (ip), 30 mg kg(-1) DMF ip, or 100 mg kg(-1) intragastrically (ig) 24 hours before IM. Intestinal transit was assessed 24 hours postoperatively and mucosa-free muscularis or whole segments of the small intestine were stored for later analysis. Intestinal HO-1 protein expression was studied at 6, 12, and 24 hours after administration of hemin or DMF in non-manipulated mice.

Key results Pretreatment with hemin and DMF, both ig and ip, prevented the delayed transit seen after IM. Concomitantly, both hemin and DMF significantly reduced the increased interleukin-6 levels and the elevated leukocyte infiltration in the muscularis. Hemin but not DMF caused a significant increase in intestinal HO-1 protein expression and co-administration of the HO-1 inhibitor chromium mesoporphyrin abolished the protective effects of hemin on POI; DMF reduced the IM-induced activation of NF-kappa B and ERK 1/2.

Conclusions and Inferences Both hemin and DMF improve the delayed transit and inflammation seen in murine POI, but only hemin does so in a HO-1-dependent manner.}},
  articleno    = {{e13624}},
  author       = {{Van Dingenen, Jonas and Pieters, Leen and Van Nuffel, Elien and Lefebvre, Romain}},
  issn         = {{1350-1925}},
  journal      = {{NEUROGASTROENTEROLOGY AND MOTILITY}},
  keywords     = {{dimethyl fumarate,heme oxygenase-1,hemin,mouse,postoperative ileus,CARBON-MONOXIDE,ISCHEMIA/REPERFUSION INJURY,SURGICAL MANIPULATION,KAPPA-B,PROTECTS,SUPPRESSES,METABOLISM,MECHANISMS,EXPRESSION,INDUCTION}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{11}},
  title        = {{Hemin reduces postoperative ileus in a heme oxygenase 1‐dependent manner while dimethyl fumarate does without heme oxygenase 1‐induction}},
  url          = {{http://doi.org/10.1111/nmo.13624}},
  volume       = {{32}},
  year         = {{2020}},
}

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