Epidermal growth factor enhances repair of rat intestinal mucosa damaged by oral administration of methotrexate.
To examine the trophic effect of epidermal growth factor on the rat small intestine, we measured diamine oxidase and ornithine decarboxylase activities in intestinal mucosa injured by methotrexate. Methotrexate was infused orally via a gastric tube at a dose of 10 mg/kg per day on 3 successive days (days 1-3). Epidermal growth factor was injected intraperitoneally at a dose of 40 micrograms/kg per day on 4 successive days following methotrexate infusion (days 4-7). Methotrexate caused a marked decrease in diamine oxidase activity; this decrease returned to a normal level on day 13 in controls. In rats injected with epidermal growth factor, diamine oxidase activity began to recover earlier than in the controls, and returned to a normal level on day 11. Epidermal growth factor enhanced the increase of ornithine decarboxylase activity in mucosa injured by methotrexate. When the increase of ornithine decarboxylase activity was suppressed by alpha-difluoromethylornithine, epidermal growth factor failed to facilitate the repair of intestinal mucosa. These results indicate that epidermal growth factor enhances intestinal repair following methotrexate infusion, and that this effect is mediated, at least in part, by ornithine decarboxylase. It is proposed that epidermal growth factor can be used clinically as a means to enhance mucosal repair of the intestine after chemotherapy with methotrexate.
Hirano
M
M
Department of Internal Medicine, Saga Medical School, Japan.
Iwakiri
R
R
Fujimoto
K
K
Sakata
H
H
Ohyama
T
T
Sakai
T
T
Joh
T
T
Itoh
M
M
D000284:Administration, Oral; D006631:Amine Oxidase (Copper-Containing) / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000518:Eflornithine / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D009955:Ornithine Decarboxylase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004815:Epidermal Growth Factor; D006631:Amine Oxidase (Copper-Containing); D009955:Ornithine Decarboxylase; D008727:Methotrexate; D000518:Eflornithine