Correlation between Plasma Glucagon-Like Peptide 2 Levels and Proliferative Makers in Small Intestinal Injury in Rats Induced by Methotrexate Administration

• Published in: Biological & Pharmaceutical Bulletin Vol. 29; no. 11; pp. 2327 - 2330
• Main Authors: Hirotani, Yoshihiko, Yamamoto, Kaoru, Ikeda, Kenji, Arakawa, Yukio, Li, Jun, Kitamura, Kazuyuki, Kurokawa, Nobuo, Tanaka, Kazuhiko
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.11.2006; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Administration, Oral; Animals; Biomarkers - analysis; Cell Proliferation; DNA - analysis; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay - methods; glucagon-like peptide 2; Glucagon-Like Peptide 2 - blood; intestinal injury; Intestinal Mucosa - chemistry; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Intestine, Small - chemistry; Intestine, Small - drug effects; Intestine, Small - pathology; Membrane Proteins - analysis; methotrexate; Methotrexate - administration & dosage; Methotrexate - blood; Methotrexate - toxicity; Mucositis - chemically induced; Mucositis - metabolism; plasma level; Rats; Weight Loss - drug effects
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.29.2327

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.