Dietary zinc supplementation and methotrexate-induced small intestinal mucositis in metallothionein-knockout and wild-type mice

Abstract

Background: Chemotherapy-induced small intestinal mucositis is a debilitating side effect of cancer chemotherapy and currently there are no effective therapies. Zinc (Zn), an essential trace element required for normal growth and development and tissue repair processes, may be a potential treatment strategy. Zn induces metallothionein (MT) which has been shown to sequester free radicals. The aim of this study was to determine the capacity for dietary Zn supplementation to ameliorate methotrexate (MTX)-induced intestinal mucositis. Methods: MT-knockout (MT-/-) and wild-type (MT+/+) mice were fed either a 10 mg/kg (control) or 400 mg/kg diet (high Zn) for 7 days  and intestinal mucositis was induced by a single injection of MTX (500 mg/kg) subcutaneously. Mice were sacrificed at 24 and 72 h (n=8/timepoint/genotype) after the MTX injection while continuing their respective diets. Daily weights were recorded and gut tissues were collected for histology, MT levels and myeloperoxidase (MPO) activity. Results: The duodenum and jejunum were significantly (p