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

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  • Hirotani Yoshihiko
    Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohatani University Department of Pharmacy, Osaka University Hospital
  • Yamamoto Kaoru
    Department of Pharmacy, Osaka University Hospital
  • Ikeda Kenji
    Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohatani University Department of Pharmacy, Osaka University Hospital
  • Arakawa Yukio
    Department of Pharmacy, Osaka University Hospital Clinical Laboratory of Practical Pharmacy, Osaka University of Pharmacetical Sciences
  • Li Jun
    Yanaihara Institute Inc.
  • Kitamura Kazuyuki
    Yanaihara Institute Inc.
  • Kurokawa Nobuo
    Department of Pharmacy, Osaka University Hospital
  • Tanaka Kazuhiko
    Department of Clinical Pharmacy & Clinical Pharmacokinetics, Osaka University of Pharmacetical Sciences

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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.

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