Effect of epidermal growth factor on experimental colitis in the rat.
The effect of epidermal growth factor on the rate of healing was examined in a rat model of colitis. Ulceration and inflammation of the distal colon were induced by a single intracolonic administration of 0.25 ml of 30% ethanol containing 30 mg of trinitrobenzenesulfonic acid. Epidermal growth factor was delivered intracolonically via the rectum or s.c. for 7 days after induction of colitis. Repeated s.c. injections of epidermal growth factor (25 and 100 micrograms/kg/12 hr) or continuous s.c. delivery with Alzet osmotic pumps (50 and 200 micrograms/kg/24 hr) significantly reduced colonic ulceration and inflammation. Epidermal growth factor significantly reduced myeloperoxidase activity in colonic tissue and there was restitution of the glandular mucosa after epidermal growth factor treatment. In contrast, daily intracolonic treatment with epidermal growth factor (25, 100 and 200 micrograms/kg/24 hr) did not significantly reduce the colonic damage. However, intracolonic delivery of 5-aminosalicylic acid (100 and 200 mg/kg/24 hr) dose-dependently reduced the colonic damage as assessed macroscopically and histologically. We conclude that systemic and not intracolonic administration of epidermal growth factor can accelerate healing of colonic ulceration and is effective in reducing inflammation in this model of colitis.
School of Pharmacy, University of Wisconsin-Madison.
M S
MS
Luck
P
P
Bass
D000636:Aminosalicylic Acids / Q000627:therapeutic use; D000818:Animals; D003092:Colitis / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D000431:Ethanol / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D019804:Mesalamine; D009195:Peroxidase / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D000636:Aminosalicylic Acids; D015777:Eicosanoids; D000431:Ethanol; D019804:Mesalamine; D004815:Epidermal Growth Factor; D014302:Trinitrobenzenesulfonic Acid; D011239:Prednisolone; D009195:Peroxidase