title: A natural tetrahydropyrimidine, ectoine, ameliorates ischemia reperfusion injury after intestinal transplantation in rats.
abstract: OBJECTIVE
  Ischemia reperfusion (I/R) injury after small bowel transplantation leads to inflammatory reactions and loss of structural integrity with subsequent graft contractile dysfunction in the early postoperative phase. The natural tetrahydropyrimidine ectoine (1-,4-,5-,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid; THP) protects the ileal mucosa and muscularis against effects of I/R injury in an experimental model of isolated graft reperfusion. The effects of THP treatment were evaluated in an established experimental intestinal transplant model.
  
  
  METHODS
  Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (6 h cold ischemia time). Perioperative THP treatment (intraluminal/intravascular) groups were compared to vehicle-treated animals (after 3 and 24 h) and non-transplanted controls (n = 5/group). Park's score defined the effects of I/R injury. The infiltration of neutrophils, monocytes and macrophages, mRNA expression of IL-6 and TNF-α, serum levels of IL-6 and NO and smooth muscle contractility were evaluated.
  
  
  RESULTS
  Improved graft outcome after intraluminal and intravascular THP treatment was defined by considerably ameliorated neutrophil infiltration and less histological signs of I/R injury (p ≤ 0.05). In the presence of THP, mRNA expression of IL-6 and TNF-α and IL-6 and NO serum levels were reduced and smooth muscle function was improved.
  
  
  CONCLUSIONS
  THP treatment offers protection against the effects of I/R injury in intestinal transplantation in vivo, however, only as supplementary treatment option.
authors.affiliation: Department of Surgery, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pech
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ohsawa
authors.forename: Michael
authors.initials: M
authors.lastname: Praktiknjo
authors.forename: Marcus
authors.initials: M
authors.lastname: Overhaus
authors.forename: Sven
authors.initials: S
authors.lastname: Wehner
authors.forename: Martin
authors.initials: M
authors.lastname: von Websky
authors.forename: Kareem
authors.initials: K
authors.lastname: Abu-Elmagd
authors.forename: Gerhild
authors.initials: G
authors.lastname: van Echten-Deckert
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Nico
authors.initials: N
authors.lastname: Schaefer
mesh_terms: D000599:Amino Acids, Diamino / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000235:genetics; D007421:Intestine, Small / Q000503:physiopathology / Q000637:transplantation*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D011183:Postoperative Complications; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics
chemical_list: D000599:Amino Acids, Diamino; D000893:Anti-Inflammatory Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C045628:ectoine