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) |
|---|---|
| Pages (from-to) | 24-36 |
| Number of pages | 13 |
| Journal | Chemotherapy |
| Volume | 60 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2014 |
| Externally published | Yes |
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Keywords
- Bovine colostrum
- Chemotherapy-induced mucositis
- Doxorubicin
- Weaned-pig model
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Drug Discovery
- Pharmacology (medical)
- Infectious Diseases
Cite this
The weaned pig as a model for doxorubicin-induced mucositis. / Martin, Jamee; Howard, Scott C.; Pillai, Asha; Vogel, Peter; Naren, Anjaparavanda P.; Davis, Steven; Ringwald-Smith, Karen; Buddington, Karyl; Buddington, Randal K.
In: Chemotherapy, Vol. 60, No. 1, 01.01.2014, p. 24-36.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The weaned pig as a model for doxorubicin-induced mucositis
AU - Martin, Jamee
AU - Howard, Scott C.
AU - Pillai, Asha
AU - Vogel, Peter
AU - Naren, Anjaparavanda P.
AU - Davis, Steven
AU - Ringwald-Smith, Karen
AU - Buddington, Karyl
AU - Buddington, Randal K.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Bovine colostrum
KW - Chemotherapy-induced mucositis
KW - Doxorubicin
KW - Weaned-pig model
UR - http://www.scopus.com/inward/record.url?scp=84908159726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908159726&partnerID=8YFLogxK
U2 - 10.1159/000365725
DO - 10.1159/000365725
M3 - Article
C2 - 25341697
AN - SCOPUS:84908159726
VL - 60
SP - 24
EP - 36
JO - Chemotherapy
JF - Chemotherapy
SN - 0009-3157
IS - 1
ER -