Optimization of the non-invasive 13C-sucrose breath test in a rat model of methotrexate-induced mucositis

Abstract

In order to determine the sensitivity and specificity of the test and to optimize experimental conditions utilizing the SBT in a rat model of chemotherapy-induced small intestinal damage. Initially, a 13C-sucrose dose-response study was performed in rats to determine an optimal sucrose concentration for the SBT; then applied to assess chemotherapy-induced intestinal damage. A further study was conducted to establish a SBT time-course of methotrexate-induced small intestinal damage and repair. Animals were killed at 96 or 144 h. A sucrose concentration of 0.25 g/ml was optimal (20% CV) for reproducibility and detection of intestinal damage. Maximal damage occurred at 72 h, small intestinal repair was initiated by 96 h and continued at 144 h post-MTX, as determined by the SBT and confirmed by biochemical analyses. Levels of sensitivity and specificity for the SBT were 98 and 94%, respectively. The SBT is a reliable non-invasive marker of small intestinal health and damage with a high degree of sensitivity and specificity.