Abstract

This study investigated the efficacy of zinc (Zn) supplementation to ameliorate methotrexate (MTX)‐induced intestinal mucositis in mice. MT‐I&‐II null (MT−/−) and wild‐type (MT+/+) mice were fed either a 10 (control) or 400 mg Zn/kg diet (high Zn) for 7 days at which time intestinal mucositis was induced by a single subcutaneous injection of MTX (500 mg/kg). Mice were sacrificed at 24 and 72 h post MTX injection while continuing their respective diets. The sucrose breath test (SBT) was used to assess small intestinal integrity and was performed prior to feeding the Zn diets, 5 days after and 24 and 72 h post MTX injection. MT+/+ mice (4.5 (1–8); median (ranges)) had significantly (p<0.05) lower histological severity scores compared to MT−/− mice (8.8 (4–13)), irrespective of Zn intake. Small bowel MTX‐induced damage, as assessed by the SBT, was significantly (p<0.05) decreased in MT+/+ (16.1 ± 1.2 cumulative % dose recovered at 90 min; mean±SEM) compared to MT−/− mice (12.4 ± 1.2), irrespective of time and diet. This was most prominent at 72 h post MTX administration (MT+/+; 11.9 ± 2.0 vs MT−/−; 7.3 ± 2.5). Dietary Zn did not ameliorate MTX‐induced gut damage in either MT+/+ or MT−/− mice as assessed by the SBT or histologically. Zn supplementation did not ameliorate MTX‐induced gut damage. The presence of MT was protective against small intestinal damaged induced by MTX, assessed by the SBT.

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