title: Hemin induction of HO-1 protects against LPS-induced septic ileus.
abstract: BACKGROUND
  Heme oxygenase (HO-1) protects against inflammation. In this study, we investigated the protective function of hemin-induced HO-1 against lipopolysaccharide (LPS)-induced ileus.
  
  
  METHODS
  Rats received LPS intraperitoneally 24 h after intraperitoneal hemin pretreatment or placebo. We also injected zinc protoporphyrin (ZnPP, 3rd group), an inhibitor of HO-1, intraperitoneally 2 h before LPS administration. To assess intestinal muscle function, we examined muscularis strip contractility in an organ bath and measured gastrointestinal transit in vivo. We investigated inflammation within the muscularis using polymerase chain reaction (interleukin [IL]-6, inducible nitric oxide synthase (iNOS), HO-1 and IL-10) 6 and 24 h after LPS.
  
  
  RESULTS
  Hemin significantly improved in vitro intestinal muscularis contractility (P < 0.001). In addition, hemin prevented LPS-induced dysmotility in vivo (gastrointestinal transit, geometric center: 8.39 ± 0.33 versus 5.68 ± 0.44; P < 0.001). In Zinc protoporphyrin (ZnPP)-treated animals, both parameters were significantly decreased compared with the hemin group. Messenger RNA expression demonstrated a significant reduction in IL-6 (6 h, hemin: 127.6 ± 36.7 versus LPS: 14,431 ± 5407; 24 h: 1.58 ± 0.39 versus 11.15 ± 2.59; P < 0.01) and iNOS (6 h: 2516 ± 985 versus 50,771 ± 13,321; 24 h: 55.11 ± 10.55 versus 257.1 ± 43.18; P < 0.001) in hemin-treated animals. Anti-inflammatory HO-1 messenger RNA levels (6 h, hemin: 116.3 ± 18.55 versus LPS: 26.02 ± 3.64; 24 h: 18.46 ± 2.69 versus 2.80 ± 0.32; P < 0.001) were increased. There was no significant difference in IL-10 levels at 6 and 24 h. ZnPP reversed the anti-inflammatory hemin effects.
  
  
  CONCLUSIONS
  Hemin induction of HO-1 diminishes LPS-induced sepsis. Heme oxygenase-1 has a central role in preventing sepsis-induced ileus. This benefit is reversed by HO-1 inhibition with ZnPP.
authors.affiliation: Department of General, Visceral, Thoracic, and Vascular Surgery, University of Bonn, Bonn, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bortscher
authors.forename: Johannes
authors.initials: J
authors.lastname: Chang
authors.forename: Tim O
authors.initials: TO
authors.lastname: Vilz
authors.forename: Nico
authors.initials: N
authors.lastname: Schäfer
authors.forename: Nils
authors.initials: N
authors.lastname: Sommer
authors.forename: Sven
authors.initials: S
authors.lastname: Wehner
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Marcus
authors.initials: M
authors.lastname: Overhaus
mesh_terms: D000818:Animals; D005772:Gastrointestinal Transit / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology*; D045823:Ileus / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications*
chemical_list: D008070:Lipopolysaccharides; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D051547:Heme Oxygenase-1