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American Journal of Clinical Nutrition, Vol. 77, No. 5, 1296-1303, May 2003
© 2003 American Society for Clinical Nutrition

Original Research Communication

Dietary supplementation with zinc and a growth factor extract derived from bovine cheese whey improves methotrexate-damaged rat intestine1,2,3

Cuong D Tran, Gordon S Howarth, Peter Coyle, Jeffrey C Philcox, Allan M Rofe and Ross N Butler

1 From the Gastroenterology Unit, Women’s and Children’s Hospital (CDT, GSH, and RNB), the Cooperative Research Centre for Tissue Growth and Repair and the Child Health Research Institute (GSH), the Department of Physiology, University of Adelaide (GSH and RNB), and the Division of Clinical Biochemistry, Institute of Medical and Veterinary Science (PC, JCP, and AMR), Adelaide, Australia.

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.

Design: 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.

Key Words: Zinc • whey growth factor extract • intestinal permeability • small-intestine damage






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