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

TY - JOUR

T1 - Doxorubicin-Induced Gut Toxicity in Piglets Fed Bovine Milk and Colostrum

AU - Shen, René L.

AU - Rathe, Mathias

AU - Jiang, Pingping

AU - Pontoppidan, Peter E. L.

AU - Heegaard, Peter M. H.

AU - Müller, Klaus

AU - Sangild, Per T.

PY - 2016/12

Y1 - 2016/12

N2 - Objective: Chemotherapy-induced intestinal toxicity is a common adverse effect of cancer treatment.Wehypothesized 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/m2) 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.

AB - Objective: Chemotherapy-induced intestinal toxicity is a common adverse effect of cancer treatment.Wehypothesized 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/m2) 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.

U2 - 10.1097/MPG.0000000000001205

DO - 10.1097/MPG.0000000000001205

M3 - Journal article

C2 - 27027906

SN - 0277-2116

VL - 63

SP - 698

EP - 707

JO - Journal of Pediatric Gastroenterology and Nutrition

JF - Journal of Pediatric Gastroenterology and Nutrition

IS - 6

ER -