The weaned pig as a model for Doxorubicin-induced mucositis

Chemotherapy. 2014;60(1):24-36. doi: 10.1159/000365725. Epub 2014 Oct 21.

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.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Disease Models, Animal
  • Doxorubicin / toxicity*
  • Eating / drug effects
  • Glucose / metabolism
  • Interleukin-10 / blood
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Mucositis / chemically induced*
  • Mucositis / pathology
  • Swine
  • Tumor Necrosis Factor-alpha / blood
  • Weight Gain / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Doxorubicin
  • Glucose