TY - JOUR
T1 - Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine
AU - Kissow, Hannelouise
AU - Viby, Niels-Erik
AU - Hartmann, Bolette
AU - Holst, Jens Juul
AU - Timm, Michael
AU - Thim, Lars
AU - Poulsen, Steen Seier
PY - 2012/7
Y1 - 2012/7
N2 - PURPOSE: 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. CONCLUSION: 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.
AB - PURPOSE: 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. CONCLUSION: 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.
U2 - 10.1007/s00280-012-1882-2
DO - 10.1007/s00280-012-1882-2
M3 - Journal article
C2 - 22729158
SN - 0943-9404
VL - 70
SP - 39
EP - 48
JO - Cancer Chemotherapy and Pharmacology, Supplement
JF - Cancer Chemotherapy and Pharmacology, Supplement
IS - 1
ER -
