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

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.

• Authors: Thomas Pech, Ichiro Ohsawa, Michael Praktiknjo, Marcus Overhaus, Sven Wehner, Martin von Websky, Kareem Abu-Elmagd, Gerhild van Echten-Deckert, Joerg C Kalff, Nico Schaefer
• Journal: Pathobiology : journal of immunopathology, molecular and cellular biology (Pathobiology) Vol. 80 Issue 2 Pg. 102-10 ( 2013) ISSN: 1423-0291 [Electronic] Switzerland
• PMID: 23108005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

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

Topics

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