Correlation between plasma glucagon-like peptide 2 levels and proliferative makers in small intestinal injury in rats induced by methotrexate administration.
Glucagon-like peptide 2 (GLP-2) is a potent intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We examined whether a relationship exists between plasma level of GLP-2 and the degree of intestinal injury induced by chemotherapeutic agents in the rat. Methotrexate (MTX) was administrated orally for 6 consecutive days at doses of 1.25, 2.5, and 5.0 mg/kg body weight per day. Mucosal samples of rat duodenum, jejunum, and ileum were used for assessment of mucosal weight, DNA and protein content. Plasma GLP-2 levels were measured on day 8. MTX significantly reduced body weight. The values of all indices tended to decrease in all segments with increases in MTX dose. Plasma GLP-2 levels were significantly higher in the MTX 2.5 mg/kg/d group (p<0.05) and the MTX 5.0 mg/kg/d group (p<0.01) than in the control group. Correlations were found between plasma GLP-2 levels and mucosal weight, DNA and protein content. We concluded that plasma GLP-2 levels reflect the degree of intestinal injury following MTX administration in this preclinical model.
Hirotani
Yoshihiko
Y
Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohatani University, Tondabayashi, Japan. hirotay@osaka-ohtani.ac.jp
Yamamoto
Kaoru
K
Ikeda
Kenji
K
Arakawa
Yukio
Y
Li
Jun
J
Kitamura
Kazuyuki
K
Kurokawa
Nobuo
N
Tanaka
Kazuhiko
K
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D049109:Cell Proliferation; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D053767:Glucagon-Like Peptide 2 / Q000097:blood*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D052016:Mucositis / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D015431:Weight Loss / Q000187:drug effects
D015415:Biomarkers; D053767:Glucagon-Like Peptide 2; D008565:Membrane Proteins; D004247:DNA; D008727:Methotrexate