Effect of IGF-I on Healing of Colonic Anastomoses in Rats Under 5-FU Treatment

• Published in: The Journal of surgical research 2008, Vol.144 (1), p.138-144
• Main Authors: Zacharakis, Emmanouil, M.D., Ph.D, Demetriades, Haralampos, M.D., Ph.D, Pramateftakis, Manousos-Georgios, M.D, Lambrou, Ioannis, M.D, Zacharakis, Evangelos, M.D, Zaraboukas, Thomas, M.D., Ph.D, Koliakos, Georgios, M.D., Ph.D, Kanellos, Ioannis, M.D., Ph.D, Betsis, Dimitrios, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: 5-FU; anastomoses; Anastomosis, Surgical; Animals; Antimetabolites, Antineoplastic - toxicity; Biological and medical sciences; Collagen - metabolism; Colon - drug effects; Colon - metabolism; Colon - surgery; Colonic Neoplasms - surgery; colorectal surgery; Drug Interactions; Fluorouracil - toxicity; General aspects; healing; Hydroxyproline - metabolism; IGF-I; Injections, Intraperitoneal; Insulin-Like Growth Factor I - pharmacology; Male; Medical sciences; Pressure; Rats; Rats, Wistar; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Surgical Wound Dehiscence - drug therapy; Surgical Wound Dehiscence - prevention & control; Tissue Adhesions - drug therapy; Tissue Adhesions - prevention & control; Wound Healing - drug effects
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2007.03.045

Background The aim of this experimental study was to investigate whether insulin-like growth factor I (IGF-I) can protect the colonic healing from the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU). Materials and methods Eighty male Wistar rats were randomized into four groups of 20 rats each. Immediately after anastomoses were performed, rats in the control group were injected with 1 mL/100 gr of intraperitoneal saline solution, which was repeated daily until killed. Rats in the 5-FU and IGF-I +5-FU groups received 5-FU in a dose of 20 mg/kg body weight intraperitoneally, from the day of operation until killed. Rats in the IGF-I and IGF-I +5-FU groups received IGF-I in a dose of 2 mg/kg body weight intraperitoneally, immediately after the colonic anastomosis was performed and on 2nd, 4th, and 6th postoperative day. Rats were sacrificed on the 7th postoperative day. Results The dehiscence rate in the 5-FU group was 30% and it was significantly higher compared with the control and the IGF-I group ( P = 0.020 for both comparisons). However, in the IGF-I +5-FU group, the dehiscence rate decreased to 10%. The administration of IGF-I resulted in a significant rise of bursting pressure in the IGF-I +5-FU group compared with the 5-FU group ( P < 0.001). There was no statistical difference in bursting pressure between the IGF-I +5-FU and control groups ( P = 1.000). The hydroxyproline levels were higher in the IGF-I and the IGF-I +5-FU groups as a result of the stimulating act of IGF-I. Conclusion IGF-I, when given intraperitoneally, seems to mediate some of the adverse effects of 5-FU on the colonic healing in rats.