Doxorubicin-Induced Gut Toxicity in Piglets Fed Bovine Milk and Colostrum

J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):698-707. doi: 10.1097/MPG.0000000000001205.


Objective: Chemotherapy-induced intestinal toxicity is a common adverse effect of cancer treatment. We hypothesized that a milk diet containing bovine colostrum (BC) would reduce intestinal toxicity in doxorubicin-treated piglets.

Methods: "Study 1" investigated intestinal parameters 9 days after a single dose of doxorubicin (1 × 75 mg/m) in piglets fed bovine milk enriched with whey protein (BM). In "study 2," responses to doxorubicin treatment were investigated in piglets receiving either 7 BC feedings per day (Only-BC, n = 13), 4 BC feedings (High-BC, n = 13), 2 BC feedings (Low-BC, n = 14), or no BC (only BM, n = 13).

Results: Doxorubicin treatment induced clinical signs of intestinal toxicity with diarrhea and weight loss, relative to controls (P < 0.05). White blood cells, hexose absorptive function, plasma citrulline, weights of intestine, colon, and spleen were reduced, whereas gut permeability and plasma C-reactive protein levels were increased (all P < 0.05). Limited or no effects were observed for digestive enzymes, proinflammatory cytokines, or tight-junction proteins in the intestine. Increasing BC supplementation to doxorubicin-treated piglets (study 2) had no consistent effects on plasma C-reactive protein and citrulline levels, intestinal morphology, digestive enzymes, permeability, or proinflammatory cytokines. Only-BC pigs, however, had lower diarrhea severity toward the end of the experiment (P < 0.05 vs BM) and across the BC groups, intestinal toxicity was reduced (P < 0.01).

Conclusions: Doxorubicin-treated piglets are relevant for studying chemotherapy-induced gut toxicity. Colostrum supplementation had limited effects on doxorubicin-induced toxicity in milk-fed piglets suggesting that colostrum and a bovine milk diet enriched with whey protein provided similar protection of the developing intestine from chemotherapy-induced toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / toxicity*
  • C-Reactive Protein
  • Cattle
  • Colostrum / drug effects*
  • Colostrum / metabolism
  • Doxorubicin / administration & dosage
  • Doxorubicin / toxicity*
  • Female
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Milk / metabolism
  • Swine
  • Weight Gain


  • Antibiotics, Antineoplastic
  • Doxorubicin
  • C-Reactive Protein