The weaned pig as a model for Doxorubicin-induced mucositis.

Abstract

BACKGROUND: Chemotherapy-induced mucositis (CIM) complicates cancer therapy and limits maximum tolerated doses and efficacy. Rodent models do not reproducibly mimic clinical CIM, so alternative models are needed. METHODS: CIM severity was assessed after weaned pigs were treated with doxorubicin (5 and 3.75 mg/kg) using clinical observations, laboratory parameters and gastrointestinal structure and functions. Bovine colostrum was provided as an experimental intervention to the pigs treated receiving the 3.75 mg/kg dose. RESULTS: Doxorubin at 3.75 mg/kg decreased food intake and weight gain (p < 0.05) and caused diarrhea and vomiting that coincided with damage to the small intestine mucosa based on histological scoring (p < 0.05). It resulted in higher serum TNF-&#x3b1; concentrations, increased chloride secretion and reduced brush border membrane disaccharidase activities and carrier-mediated glucose uptake (all p < 0.05). The gastrointestinal damage and dysfunction resemble the clinical and laboratory features of CIM in humans; these can be partially prevented by providing cow colostrum. CONCLUSION: The weaned pig is a relevant large animal for studying CIM and evaluating existing and experimental interventions for mucositis.