Biol. Pharm. Bull. 29(11) 2327—2330 (2006)

apy for cancer patients. The cytotoxicity of antineoplastic agents affects not only tumor cells but also rapidly proliferating normal cells, such as those of the gastrointestinal mucosa. Common complications of chemotherapy thus include stomatitis and enterocolitis. Methotrexate (MTX) is an antimetabolite drug that blocks the production of biologically active forms of folic acid. The major lesions resulting from its cytotoxic effects occur in bone marrow and the intestinal tract. High doses of MTX cause severe enterocolitis, weight loss, anorexia and intestinal atrophy. The mucosa of the digestive tract, particularly that of the small intestine, is a critical site of action of anticancer agents including MTX, as the undifferentiated epithelial cells in the crypts, which ensure continuous and relatively fast regeneration of the epithelium, are particularly sensitive to these cytostatic drugs. Patients receiving these anticancer agents frequently experience gastrointestinal side effects, such as nausea, vomiting and diarrhea, reflecting gastrointestinal mucosal damage or enterocolitis. Chemotherapy-associated diarrhea may be problematic, and even life threatening, if complicated by mucosal ulceration and inflammatory changes. Moreover, patients with advanced malignancy often suffer from malnutrition, which increases toxicity and decreases tumor responses to treatment, and such conditions can be dose limiting in therapeutic regimens. A method for prediction of adverse reactions to chemotherapy is thus needed to avoid their occurrence. Gastrointestinal mucosal integrity is regulated by several growth factors and cytokines, such as transforming growth factors-beta and IL-11. Glucagon-like peptide 2 (GLP-2) has been demonstrated to have intestinotrophic effects. GLP-2, a 33-amino acid peptide member of a family of proglucagon-derived peptides (PGDP) that also includes enteroglucagon, is secreted from L-type entero-endocrine cells of the distal small intestine and colon. GLP-2 increases crypt cell proliferation and decreases the rate of apoptosis in small intestinal epithelium. Acute or chronic administration of GLP-2 induces functional changes in the intestine, improving its capacity for nutrient absorption. In addition, GLP-2 treatment has been shown to enhance intestinal adaptation following major small bowel resection, to prevent TPN-induced atrophy, and to reduce the severity of dextran sulfate-induced colitis and indomethacin-induced enteritis in animal models. On the other hand, plasma GLP-2 levels appear to vary with intestinal mucosal condition and injury. However, although changes in various conditions of the intestinal mucosa are now being widely studied, the relationship between plasma GLP-2 levels and intestinal mucosal injury induced by various drugs, including antineoplastic agents, has yet to be clearly determined. Moreover, no standard methods of diagnosis or therapeutic protocols exist for chemotherapy-induced enteritis, and further research into new therapeutic avenues for treatment or prevention of this intestinal injury is needed. The present study examined the relationship between plasma GLP-2 levels and changes in proliferative markers resulting from MTX-induced intestinal mucositis.