Pre-treatment with insulin-like growth factor-I partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats.
Insulin-like growth factor-I (IGF-I) has been demonstrated to enhance mucosal repair following intestinal damage induced by chemotherapeutic agents (intestinal mucositis). However, the potential for prophylactic IGF-I to protect the intestine remains undefined. We investigated the effects of IGF-I pre-treatment on chemotherapy-induced mucositis in rats. Male Sprague Dawley rats were treated for 7 days with 0 or 4.3mg/kg/day IGF-I delivered systemically via osmotic mini-pump. Rats received an intraperitoneal injection of 0 or 150 mg/kg 5-fluorouracil (5-FU) on day 7 and were killed 48 h later for assessment of intestinal damage and repair. Compared to normal controls, 5-FU decreased epithelial proliferation by 86%, concurrently increasing the incidence of apoptosis 87-fold, whilst decreasing small intestinal (SI) length by 14%, SI weight by 30% and total gut weight by 24%. 5-FU decreased villus height in the duodenum (23%), jejunum (20%) and ileum (30%) with crypt depths decreased by 31%, 27% and 33% in these gut regions. These effects were less profound in IGF-I pre-treated rats in which apoptosis was increased 48-fold, with SI length decreased by 7%, SI weight by 18% and total gut weight by 15% accompanied by decreases in villus height of 8% (duodenum), 14% (jejunum) and 21% (ileum), and crypt depth decreases of 23%, 16% and 17% for the same gut regions, compared to normal controls. We conclude that IGF-I pre-treatment only partially attenuates features of intestinal mucositis when assessed 48 h after 5-FU chemotherapy.
Cool
Johanna C
JC
Cooperative Research Centre for Tissue Growth and Repair, Australia.
Dyer
Jodie L
JL
Xian
Cory J
CJ
Butler
Ross N
RN
Geier
Mark S
MS
Howarth
Gordon S
GS
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D004396:Coloring Agents / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects; D005472:Fluorouracil / Q000009:adverse effects / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013393:Sucrase / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D004396:Coloring Agents; D013395:Sucrose; D007334:Insulin-Like Growth Factor I; D013393:Sucrase; D001973:Bromodeoxyuridine; D005472:Fluorouracil