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Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage

Citation

Berlanga, J and Prats, P and Remirez, D and Gonzalez, R and Lopez-Saura, P and Aguiar, J and Ojeda, M and Boyle, JJ and Fitzgerald, AJ and Playford, RJ, Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage, American Journal of Pathology, 161, (2) pp. 373-379. ISSN 0002-9440 (2002) [Refereed Article]

DOI: doi:10.1016/S0002-9440(10)64192-2

Abstract

Ischemia/reperfusion of mesenteric vessels is a useful model for acute vascular insufficiency and the early stages of multiorgan failure, conditions associated with high morbidity and mortality. Epidermal growth factor (EGF) is a potent mitogen that shows potential for use in intestinal injury. We therefore examined its influence on this model. Male Sprague-Dawley rats received human recombinant EGF (2 mg/kg i.p., n = 14) or saline (n = 16); 25 minutes before arterial clamping of the superior mesenteric artery (ischemic period) for 60 minutes followed by a final 60-minute reperfusion period. Additional rats were not operated on (controls, n = 7) or had sham operation (laparotomy only, n = 10). Ischemia/reperfusion caused macroscopic damage affecting 56%, 51 to 67% (median, interquartile range), of small intestinal length and intraluminal bleeding. Malondialdehyde levels (free radical marker) increased eightfold compared to non-operated animals (2400, 2200 to 2700 μmol/mg protein versus 290, 250 to 350 μmol/mg protein, P < 0.01) and myeloperoxidase levels (marker for inflammatory infiltrate) increased 15-fold (3150, 2670 to 4180 U/g tissue versus 240, 190 to 250 U/g tissue, P < 0.01). Pretreatment with EGF reduced macroscopic injury to 11%, 0 to 15%; prevented intraluminal bleeding; and reduced malondialdehyde and myeloperoxidase levels by ∼60% and 90% (all P < 0.01 versus non-EGF-treated). Mesenteric ischemia/reperfusion also damaged the lungs and kidneys and increased serum tumor necrosis factor-α levels (circulating cytokine activity marker). EGF pretreatment also reduced these changes. These studies provide preliminary evidence that EGF is a novel therapy for the early treatment or prevention of intestinal damage and multiorgan failure resulting from mesenteric hypoperfusion.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Gastroenterology and Hepatology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
Author:Playford, RJ (Professor Ray Playford)
ID Code:72903
Year Published:2002
Web of Science® Times Cited:52
Deposited By:Research Division
Deposited On:2011-09-02
Last Modified:2011-09-20
Downloads:0

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