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Updated: Aug 24, 2026

Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease
Published on: February 9, 2016
Lactoferrin reduces methotrexate-induced small intestinal damage, possibly through inhibition of GLP-2-mediated
Belinda van't Land1, Noortje M A van Beek, Jeroen J M van den Berg
1Department of Condition and Disease Specific Research, Numico-Research, PO Box 7005, 6700 CA Wageningen, Wageningen, The Netherlands.
Abstract:
A strategy protecting the small intestine against deleterious side effects associated with anti-cancer therapy is arresting epithelial cell cycling temporally. Since endogenous glucagon-like peptide-2 (GLP-2) is a trophic factor specific for intestinal epithelia, the possibility of inhibiting GLP-2-mediated cell proliferation by lactoferrin, thereby protecting the small intestine against deleterious side effects of anticancer therapy, was investigated. In Caco-2 cells, GLP-2-mediated proliferation was reduced in a dose-dependent manner using lactoferrin. Furthermore, in a rat model for methotrexate-induced mucositis, lactoferrin reduced BrdU incorporation in small intestinal epithelial cells, indicating inhibition of epithelial cell proliferation in vivo. Subsequently, protection against methotrexate-induced intestinal damage was found in corresponding regions. These results show, for the first time, that lactoferrin interferes with GLP-2-induced intestinal epithelial proliferation. It may therefore be hypothesized that lactoferrin protects the intestine against anticancer therapy-induced intestinal damage, via inhibition of GLP-2-induced small intestinal epithelial cell proliferation.
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