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

René L. Shen; Mathias Rathe; Pingping Jiang; Peter E. L. Pontoppidan; Peter M. H. Heegaard; Klaus Müller; Per T. Sangild

doi:10.1097/MPG.0000000000001205

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

René L. Shen, Mathias Rathe, Pingping Jiang, Peter E. L. Pontoppidan, Peter M. H. Heegaard, Klaus Müller, Per T. Sangild

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Pediatric Gastroenterology and Nutrition
Volume	63
Issue number	6
Pages (from-to)	698-707
Number of pages	10
ISSN	0277-2116
DOIs	https://doi.org/10.1097/MPG.0000000000001205
Publication status	Published - Dec 2016

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title = "Doxorubicin-Induced Gut Toxicity in Piglets Fed Bovine Milk and Colostrum",

abstract = "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.",

author = "Shen, {Ren{\'e} L.} and Mathias Rathe and Pingping Jiang and Pontoppidan, {Peter E. L.} and Heegaard, {Peter M. H.} and Klaus M{\"u}ller and Sangild, {Per T.}",

year = "2016",

month = dec,

doi = "10.1097/MPG.0000000000001205",

language = "English",

volume = "63",

pages = "698--707",

journal = "Journal of Pediatric Gastroenterology and Nutrition",

issn = "0277-2116",

publisher = "Lippincott Williams & Wilkins",

number = "6",

}

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 -

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

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