A natural tetrahydropyrimidine, ectoine, ameliorates ischemia reperfusion injury after intestinal transplantation in rats

Pathobiology. 2013;80(2):102-10. doi: 10.1159/000342792. Epub 2012 Oct 27.

Abstract

Background/aims: 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.

Conclusion: THP treatment offers protection against the effects of I/R injury in intestinal transplantation in vivo, however, only as supplementary treatment option.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Diamino / administration & dosage*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Interleukin-6 / genetics
  • Intestine, Small / physiopathology
  • Intestine, Small / transplantation*
  • Macrophages / immunology
  • Male
  • Monocytes / immunology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Neutrophil Infiltration
  • Neutrophils / immunology
  • Nitric Oxide / metabolism
  • Postoperative Complications
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury / etiology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Transplantation, Isogeneic
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Amino Acids, Diamino
  • Anti-Inflammatory Agents
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • ectoine