Glucagon-like peptide-2 improves both acute and late experimental radiation enteritis in the rat.
OBJECTIVE
Acute and/or chronic radiation enteritis can develop after radiotherapy for pelvic cancers. Experimental and clinical observations have provided evidence of a role played by acute mucosal disruption in the appearance of late effects. The therapeutic potential of acute administration of glucagon-like peptide-2 (GLP-2) against acute and chronic intestinal injury was investigated in this study.


METHODS
Intestinal segments were surgically exteriorized and exposed to 16.7 or 19 Gy X-rays. The rats were treated once daily with vehicle or a protease-resistant GLP-2 derivative for 14 days before irradiation, with or without 7 days of GLP-2 after treatment. Macroscopic and microscopic observations were made 2 and 15 weeks after radiation exposure.


RESULTS
In the control animals, GLP-2 induced an increase in intestinal mucosal mass, along with an increase in villus height and crypt depth. GLP-2 administration before and after irradiation completely prevented the acute radiation-induced mucosal ulcerations observed after exposure to 16.7 Gy. GLP-2 treatment strikingly reduced the late radiation damage observed after 19 Gy irradiation. Microscopic observations revealed an improved organization of the intestinal wall and an efficient wound healing process, especially in the smooth muscle layers.


CONCLUSIONS
GLP-2 has a clear therapeutic potential against both acute and chronic radiation enteritis. This therapeutic effect is mediated through an increased mucosal mass before tissue injury and the stimulation of still unknown mechanisms of tissue response to radiation damage. Although these preliminary results still need to be confirmed, GLP-2 might be a way to limit patient discomfort during radiotherapy and reduce the risk of consequential late effects.
Radiosensibilité des Tumeurs et des Tissus Sains, UPRES EA-2710, Institut de Radioprotection et de Sûreté Nucléaire/Institut Gustave Roussy, Villejuif, France.
Sandra
S
Torres
Lars
L
Thim
Fabien
F
Milliat
Marie-Catherine
MC
Vozenin-Brotons
Ulfe Bang
UB
Olsen
Ian
I
Ahnfelt-Rønne
Jean
J
Bourhis
Marc
M
Benderitter
Agnès
A
François
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004353:Drug Evaluation, Preclinical; D004751:Enteritis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D053767:Glucagon-Like Peptide 2 / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000473:pathology / Q000528:radiation effects; D007421:Intestine, Small / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D053767:Glucagon-Like Peptide 2