Glucagon-like peptide 2: a new treatment for chemotherapy-induced enteritis.
BACKGROUND
Glucagon-like peptide 2 (GLP-2) is a recently identified intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We hypothesized that GLP-2 administration would be beneficial in chemotherapy-induced enteritis either by preventing injury or by promoting recovery.


METHODS
Rats received no drug (control), chemotherapy alone [5-fluorouracil (5-FU), 190 mg/kg, ip] (Chemo), 5-FU followed by 3 days of GLP-2 analog (ALX-0600, 0.1 microg, sc twice daily) (CH-G), or GLP-2 analog for 6 days prior to 5-FU and for 3 days afterward (G-CH-G). Animals were pair fed. Rats received 5-bromo-2-deoxyuridine (Br-dU, 50 mg/kg, 2.5 h prior to sacrifice on Day 3 postchemotherapy) for immunohistochemical assessment of cellular proliferation.


RESULTS
Chemotherapy induced significant reductions in body weight, villus height, and crypt depth compared with controls. Intestinal wet weight, villus height, and crypt depth were significantly higher for the CH-G group compared with the Chemo group. The CH-G group also showed a significant improvement in villus height compared with the G-CH-G group. Crypt depth, but not jejunal wet weight or villus height, was significantly improved in the G-CH-G group compared with the Chemo group. The percentage of Br-dU-labeled cells in the intestinal crypts did not differ among the groups.


CONCLUSIONS
These results suggest, for the first time, that GLP-2 treatment initiated after chemotherapy administration enhances intestinal recovery. In contrast, GLP-2 treatment initiated prior to chemotherapy administration to prevent injury has less beneficial effect. GLP-2 administration may be beneficial to patients suffering from chemotherapy-induced enteritis.
Tavakkolizadeh
A
A
Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Shen
R
R
Abraham
P
P
Kormi
N
N
Seifert
P
P
Edelman
E R
ER
Jacobs
D O
DO
Zinner
M J
MJ
Ashley
S W
SW
Whang
E E
EE
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000032:analysis; D004751:Enteritis / Q000139:chemically induced* / Q000188:drug therapy*; D005472:Fluorouracil / Q000009:adverse effects*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D007583:Jejunum / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D008297:Male; D009017:Morbidity; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000964:Antimetabolites, Antineoplastic; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides; D001973:Bromodeoxyuridine; D005472:Fluorouracil