Influence of orally administered epidermal growth factor on normal and damaged intestinal mucosa in rats.
The effect of orally administered epidermal growth factor (EGF) on the mucosal growth and hydrolase activity of normal and damaged small intestine was examined in rats. Adult rats fed EGF daily at 10 times the estimated daily intake of EGF from human milk showed increases in specific activity but not total activity of various brush-border hydrolases with unaffected mucosal protein content and villus-to-crypt ratios through day 9. Ingestion of EGF for 13 days resulted in significant decreases in mucosal protein content without changes in villus height or hydrolase activity. The effect of oral EGF on recovery of damaged intestine was studied in rats fed a liquid diet supplemented with EGF at 0, 1, 10, or 20 times the estimated daily intake from human milk after treatment with methotrexate (MTX) to induce acute intestinal injury. Animals treated with MTX showed significant reductions in body weight and small intestinal villus height, mucosal protein content, and hydrolase activities through day 6 posttreatment. Daily ingestion of EGF did not affect the MTX-induced reductions in mucosal protein content and hydrolase activity by day 3 but caused significant increases in mucosal disaccharidase and leucine aminopeptidase activity by day 6 at the 1- or 10-times human milk EGF levels. Similar changes were not observed in MTX-treated rats fed the 20-times human milk level of EGF. These studies suggest that oral EGF is capable of modulating mucosal protein levels and stimulating enterocyte hydrolase expression during repair of the intestinal mucosa.
Petschow
B W
BW
Mead Johnson Research Center, Bristol-Myers Squibb, Evansville, Indiana 47721.
Carter
D L
DL
Hutton
G D
GD
D000284:Administration, Oral; D000818:Animals; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology; D007410:Intestinal Diseases / Q000139:chemically induced / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D008727:Methotrexate; D051381:Rats; D017207:Rats, Sprague-Dawley
D004815:Epidermal Growth Factor; D008727:Methotrexate