Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine.
OBJECTIVE
Gastrointestinal mucositis is an unwanted and often dose-limiting side effect to most cancer treatments. Glucagon-like peptide-2 (GLP-2) is a peptide secreted from intestinal L-cells in response to nutrient intake. The peptide is involved in the regulation of apoptosis and proliferation in the intestine. We aimed to investigate the role of GLP-2 in experimental chemotherapy-induced mucositis. METHODS STUDY 1: Rats were given a single injection with 5-fluorouracil (5-FU) and killed in groups of five each day for 5 days. Blood samples were analysed for GLP-2 concentrations. The intestine was analysed for weight loss, morphometric estimates and proliferation. STUDY 2: Rats were treated with GLP-2 or control vehicle 2 days before a single injection of 5-FU or saline. The treatments continued until kill 2 days after. The intestine was investigated for influx of myeloperoxidase (MPO)-positive cells and morphometric estimates, such as villus height, as a marker of mucositis. RESULTS STUDY 1: Two days after chemotherapy, there was a rise in endogenous GLP-2, followed by a marked increase in proliferation. STUDY 2: Exogenous GLP-2 was able to protect the intestine from severe weight loss and completely prevented the reduction in villus height in the control rats. Furthermore, there was a significant decrease in influx of MPO-positive cells in the GLP-2-treated rats.


CONCLUSIONS
GLP-2 is secreted from the intestine in response to intestinal injury, probably explaining the compensatory hyperproliferation after chemotherapy. Exogenous GLP-2 can protect the mucosa from chemotherapy-induced mucositis in rats.
Department of Biomedical Sciences, Faculty of Health Science, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. kissow@sund.ku.dk
Hannelouise
H
Kissow
Niels-Erik
NE
Viby
Bolette
B
Hartmann
Jens Juul
JJ
Holst
Michael
M
Timm
Lars
L
Thim
Steen Seier
SS
Poulsen
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000633:toxicity*; D053767:Glucagon-Like Peptide 2 / Q000097:blood / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D052016:Mucositis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D053767:Glucagon-Like Peptide 2; D009195:Peroxidase; D005472:Fluorouracil