title: The weaned pig as a model for Doxorubicin-induced mucositis.
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.
  
  
  CONCLUSIONS
  The weaned pig is a relevant large animal for studying CIM and evaluating existing and experimental interventions for mucositis.
authors.affiliation: Department of Health and Sport Sciences, University of Memphis, Memphis, Tenn., USA.
authors.forename: Jamee
authors.initials: J
authors.lastname: Martin
authors.forename: Scott C
authors.initials: SC
authors.lastname: Howard
authors.forename: Asha
authors.initials: A
authors.lastname: Pillai
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Anjaparavanda P
authors.initials: AP
authors.lastname: Naren
authors.forename: Steven
authors.initials: S
authors.lastname: Davis
authors.forename: Karen
authors.initials: K
authors.lastname: Ringwald-Smith
authors.forename: Karyl
authors.initials: K
authors.lastname: Buddington
authors.forename: Randal K
authors.initials: RK
authors.lastname: Buddington
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D052016:Mucositis / Q000139:chemically induced* / Q000473:pathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004317:Doxorubicin; D005947:Glucose