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-α 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.
Original language | English (US) |
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Pages (from-to) | 24-36 |
Number of pages | 13 |
Journal | Chemotherapy |
Volume | 60 |
Issue number | 1 |
DOIs | |
State | Published - May 22 2014 |
Externally published | Yes |
Keywords
- Bovine colostrum
- Chemotherapy-induced mucositis
- Doxorubicin
- Weaned-pig model
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Drug Discovery
- Pharmacology (medical)
- Infectious Diseases