Effect of IGF-I on healing of colonic anastomoses in rats under 5-FU treatment.
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).


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.


CONCLUSIONS
IGF-I, when given intraperitoneally, seems to mediate some of the adverse effects of 5-FU on the colonic healing in rats.
Zacharakis
Emmanouil
E
4th Academic Surgical Unit, Aristotle University of Thessaloniki, G. Papanikolaou General Hospital, Makedonia, Greece. manoszacharakis@hotmail.com
Demetriades
Haralampos
H
Pramateftakis
Manousos-Georgios
MG
Lambrou
Ioannis
I
Zacharakis
Evangelos
E
Zaraboukas
Thomas
T
Koliakos
Georgios
G
Kanellos
Ioannis
I
Betsis
Dimitrios
D
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D003110:Colonic Neoplasms / Q000601:surgery; D004347:Drug Interactions; D005472:Fluorouracil / Q000633:toxicity*; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D013529:Surgical Wound Dehiscence / Q000188:drug therapy / Q000517:prevention & control; D000267:Tissue Adhesions / Q000188:drug therapy / Q000517:prevention & control; D014945:Wound Healing / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D006909:Hydroxyproline; D005472:Fluorouracil