Insulin-like growth factor-I (IGF-I) stimulates regrowth of the damaged intestine in rats, when administered following, but not concurrent with, methotrexate.
BACKGROUND
We tested the ability of insulin-like growth factor-I (IGF-I) to reduce damage to the intestinal mucosa (mucositis) in rats injected with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withdrawal of methotrexate.


METHODS
Rats were injected with methotrexate at the start of days 1, 2 and 3. IGF-I was infused for 5 days, commencing at the start of day 1 [concurrent administration] or at the start of day 4 [post-methotrexate administration].


RESULTS
IGF-I administered coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered post methotrexate stimulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus height and ileal crypt depth respectively.


CONCLUSIONS
Following intestinal damage of methotrexate, IGF-I primarily induced growth of the distal small intestine. The ineffectiveness of concurrently administered IGF-I may have represented an IGF-I induced recruitment of proliferating epithelial cells to the anti-proliferative effects of methotrexate.
Howarth
G S
GS
Cooperative Research Center for Tissue Growth and Repair, North Adelaide, South Australia. ghowarth@medicine.adelaide.edu.au
Cool
J C
JC
Bourne
A J
AJ
Ballard
F J
FJ
Read
L C
LC
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D004247:DNA / Q000032:analysis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D009929:Organ Size; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D013393:Sucrase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D018969:Insulin-Like Growth Factor Binding Proteins; D011506:Proteins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D013393:Sucrase; D008727:Methotrexate