The weaned pig as a model for doxorubicin-induced mucositis

Jamee Martin, Scott C. Howard, Asha Pillai, Peter Vogel, Anjaparavanda P. Naren, Steven Davis, Karen Ringwald-Smith, Karyl Buddington, Randal K. Buddington

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 languageEnglish (US)
Pages (from-to)24-36
Number of pages13
JournalChemotherapy
Volume60
Issue number1
DOIs
StatePublished - May 22 2014
Externally publishedYes

Keywords

  • Bovine colostrum
  • Chemotherapy-induced mucositis
  • Doxorubicin
  • Weaned-pig model

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Pharmacology (medical)
  • Infectious Diseases

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