Dietary supplementation with zinc and a growth factor extract derived from bovine cheese whey improves methotrexate-damaged rat intestine.
BACKGROUND
Oral administration of zinc or bovine whey-derived growth factor extract (WGFE) is known to reduce intestinal permeability and ameliorate methotrexate (MTX)-induced mucositis, respectively.


OBJECTIVE
We examined the effects of zinc, WGFE, and zinc plus WGFE on gut damage in MTX-treated rats.


METHODS
Rats (n = 16/group) were fed zinc (1000 mg/kg diet), WGFE (32 mg/kg diet), zinc plus WGFE, or control (10 mg Zn/kg diet) diets for 7 d and then injected subcutaneously with MTX (2.5 mg/kg) for 3 d to induce gut damage. Gut histology and intestinal permeability were assessed.


RESULTS
The Zn+WGFE diet was associated with both reduced gut damage on day 5 and enhanced recovery on day 7. The WGFE diet ameliorated gut damage, whereas the Zn and Zn+WGFE diets enhanced repair. Gut metallothionein and tissue zinc concentrations were significantly (P < 0.01) higher with Zn and Zn+WGFE on days 5 and 7 than without zinc supplementation. The Zn and Zn+WGFE diets significantly (P < 0.05) decreased gut permeability on days 3-4 compared with the control diet. Intestinal permeability was significantly (P < 0.05) increased on days 5-6. On days 6-7, only the WGFE diet improved gut permeability (by 80%) compared with the control diet.


CONCLUSIONS
Dietary administration of WGFE and a pharmacologic dose of zinc reduced intestinal damage and enhanced recovery, respectively. WGFE also improved gut permeability after MTX-induced bowel damage. In combination, zinc and WGFE hastened repair of gut damage, which may have clinical application in chemotherapy-induced mucositis.
Tran
Cuong D
CD
Gastroenterology Unit, Women's and Children's Hospital, University of Adelaide, Adelaide, Australia. tranc@mail.wch.sa.gov.au
Howarth
Gordon S
GS
Coyle
Peter
P
Philcox
Jeffrey C
JC
Rofe
Allan M
AM
Butler
Ross N
RN
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D002417:Cattle; D002611:Cheese; D019587:Dietary Supplements; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000032:analysis; D008727:Methotrexate / Q000633:toxicity; D008894:Milk Proteins / Q000737:chemistry; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D000067816:Whey Proteins; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D006133:Growth Substances; D008894:Milk Proteins; D000067816:Whey Proteins; D008668:Metallothionein; D015032:Zinc; D008727:Methotrexate