title: Milk diets influence doxorubicin-induced intestinal toxicity in piglets.
abstract: Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated with doxorubicin (DOX) treatment. Five-day-old pigs were administered DOX (1 × 100 mg/m(2)) or an equivalent volume of saline (SAL) and either fed formula (DOX-Form, n = 9, or SAL-Form, n = 7) or bovine colostrum (DOX-Colos, n = 9, or SAL-Colos, n = 7). Pigs were euthanized 5 days after initiation of chemotherapy to assess markers of small intestinal function and inflammation. All DOX-treated animals developed diarrhea, growth deficits, and leukopenia. However, the intestines of DOX-Colos pigs had lower intestinal permeability, longer intestinal villi with higher activities of brush border enzymes, and lower tissue IL-8 levels compared with DOX-Form (all P < 0.05). DOX-Form pigs, but not DOX-Colos pigs, had significantly higher plasma C-reactive protein, compared with SAL-Form. Plasma citrulline was not affected by DOX treatment or diet. Thus a single dose of DOX induces intestinal toxicity in preweaned pigs and may lead to a systemic inflammatory response. The toxicity is affected by type of enteral nutrition with more pronounced GI toxicity when formula is fed compared with bovine colostrum. The results indicate that bovine colostrum may be a beneficial supplementary diet for children subjected to chemotherapy and subsequent intestinal toxicity.
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Rene L
authors.initials: RL
authors.lastname: Shen
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Peter E L
authors.initials: PE
authors.lastname: Pontoppidan
authors.affiliation: Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark;
authors.forename: Mathias
authors.initials: M
authors.lastname: Rathe
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Pingping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Carl Frederik
authors.initials: CF
authors.lastname: Hansen
authors.affiliation: Department of Health and Sport Sciences, University of Memphis, Memphis, Tennessee;
authors.forename: Randal K
authors.initials: RK
authors.lastname: Buddington
authors.affiliation: National Veterinary Institute, Technical University of Denmark, Lyngby, Denmark;
authors.forename: Peter M H
authors.initials: PM
authors.lastname: Heegaard
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and Institute of Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Müller
authors.affiliation: Section of Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science/Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and pts@sund.ku.dk.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic; D002097:C-Reactive Protein / Q000378:metabolism; D002417:Cattle; D003126:Colostrum / Q000378:metabolism*; D004195:Disease Models, Animal; D004317:Doxorubicin; D004750:Enteral Nutrition / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006801:Humans; D041943:Infant Formula / Q000633:toxicity*; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008871:Microvilli / Q000201:enzymology / Q000473:pathology; D052016:Mucositis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009752:Nutritional Status; D010539:Permeability; D034421:Sus scrofa; D015430:Weight Gain
chemical_list: D000903:Antibiotics, Antineoplastic; D018836:Inflammation Mediators; D016209:Interleukin-8; D004317:Doxorubicin; D002097:C-Reactive Protein
keywords: bovine colostrum; chemotherapy-induced mucositis; enteral nutrition; intestinal toxicity; milk