The weaned pig as a model for doxorubicin-induced mucositis

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

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Mucositis
Doxorubicin
Swine
Drug Therapy
Colostrum
Disaccharidases
Maximum Tolerated Dose
Microvilli
Small Intestine
Weight Gain
Vomiting
Chlorides
Diarrhea
Rodentia
Mucous Membrane
Eating
Glucose
Membranes
Serum
Neoplasms

All Science Journal Classification (ASJC) codes

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

Cite this

The weaned pig as a model for doxorubicin-induced mucositis. / Martin, Jamee; Howard, Scott; Pillai, Asha; Vogel, Peter; Naren, Anjaparavanda P.; Davis, Steven; Ringwald-Smith, Karen; Buddington, Karyl; Buddington, Randal.

In: Chemotherapy, Vol. 60, No. 1, 22.05.2014, p. 24-36.

Research output: Contribution to journalArticle

Martin, J, Howard, S, Pillai, A, Vogel, P, Naren, AP, Davis, S, Ringwald-Smith, K, Buddington, K & Buddington, R 2014, 'The weaned pig as a model for doxorubicin-induced mucositis', Chemotherapy, vol. 60, no. 1, pp. 24-36. https://doi.org/10.1159/000365725
Martin J, Howard S, Pillai A, Vogel P, Naren AP, Davis S et al. The weaned pig as a model for doxorubicin-induced mucositis. Chemotherapy. 2014 May 22;60(1):24-36. https://doi.org/10.1159/000365725
Martin, Jamee ; Howard, Scott ; Pillai, Asha ; Vogel, Peter ; Naren, Anjaparavanda P. ; Davis, Steven ; Ringwald-Smith, Karen ; Buddington, Karyl ; Buddington, Randal. / The weaned pig as a model for doxorubicin-induced mucositis. In: Chemotherapy. 2014 ; Vol. 60, No. 1. pp. 24-36.
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