Reduction of peritoneal adhesions by sustained and local administration of epidermal growth factor

Abstract

Previous studies have shown epidermal growth factor (EGF) facilitate peritoneal membrane healing by augmenting cell adhesion and migration. The objective of this study was to show the effect of sustained and local administration of EGF on peritoneal adhesion. Fourty-two rats were divided into six groups: control 7 and 14, gelatin 7 and 14, and EGF 7 and 14. Adhesions were created by scraping the cecum with mesh gause followed by application of absolute alcohol and placement of silk suture in the parietal peritoneum. The anterior walls of the intestines were covered with 5 x 5 cm unloaded, and EGF loaded gelatin films in the gelatin and EGF groups, respectively. The rats were killed on days 7 and 14 to assess the adhesion occurring, and for biochemical examination. The mean adhesion grades of EGF groups were significantly lower than in the other groups (P < 0.008). The mean adenosine deaminase (ADA) measurements of EGF 7 group were lower than in the gelatin 7 and control 7 groups but the difference was not significant (P > 0.008). The mean ADA measurements in the 14 days groups were as follows: control 14 < EGF 14 < gelatin 14 groups. The mean ADA measurements between 14 days groups did not significantly differ from each other (P > 0.008). The mean hydroxyproline measurements did not differ among the groups (P > 0.008). EGF decreased intestinal adhesion in our study. EGF has important roles in DNA synthesis and cell proliferation. Further studies are required to determine the exact mechanism by which EGF lowers the efficiency of intestinal adhesion.

The Influence of Enzymes on Adhesive Processes in the Abdominal Cavity

“…Five visual fi elds were observed randomly at 400 × magnifi cation by light microscopy and the number of positive cells out of 500 endothelial cells was counted. Semi-quantitative evaluation based on the proportion of positive cells was performed, using the criteria formulated at the Beijing seminar on standardization of immunohistochemistry techniques and diagnosis [24] : 0 -25 % : negative ( − ); 26 -50 % : low positive ( + ); 51 -75 % : medium positive ( + + ); 76 -100 % : strongly positive ( + + + ).…”

“…This fi brin deposition may lead to intra-abdominal adhesions, which are the main cause of intestinal obstructions. In spite of the advances in the treatment of intraperitoneal adhesions, the rate of complications and progression to intestinal obstruction is still unacceptably high [10,13,24] . Few trials of angiogenic agents such as VEGF (Vascular Endothelial Growth Factor), bFGF (basic Fibroblast Growth Factor) and laminins in abdominal surgery have been carried However, the advent of targeted, specifi c agents as a directed therapy against infl ammatory and neoangiogenesis raises the prospect of a new approach for anti-adhesion strategies.…”

Abdominal Adhesions: Current and Novel Therapies

“…Inhibit extracellular mediators that may enhance inflammatory or fibrotic processes Anti-TGF-b1 and TGF-b2 antibodies deceased adhesion formation in rats and mice [235,236] Anti-TGF-b1 antibody reduced cellularity of adhesions in rats, not incidence [237] Monotherapy with anti-IL-1 antibody decreased adhesions in rat model [238] Therapy with anti-IL-1 and anti-TNF-a antibodies decreased adhesions in rat model; effect superior to either monotherapy [238] sunitinib (vascular endothelial growth factor receptor 2 antagonist) reduced adhesion formation in mice [239] Epidermal growth factor Possibly increase cell proliferation and accelerate healing process Some efficacy in rat model [240] Did not affect hydroxyproline content of tissue [240] Angiotensin-converting enzyme inhibitors (ACE-I) (Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril)…”

Intra-abdominal adhesions: Anatomy, physiology, pathophysiology, and treatment

“…The result was thought secondary to the augmentation of mesothelial cell adhesion and migration by EGF (242). Underscoring the importance of VEGF in adhesion formation are two studies using anti-VEGF therapy in experimental models and demonstrating a marked reduction in adhesion formation following such intervention (243,244) Although poorly understood, local anesthetic agents have been used for proposed anti- intraperitoneally, it is not effective when given systemically.…”