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Journal of Parenteral and Enteral Nutrition
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Dietary Manipulation of Methotrexate-Induced Enterocolitis

Jian Shou, M.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

Michael D. Lieberman, M.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

Kurt Hofmann, M.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

Pablo Leon, M.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

H. Paul Redmond, M.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

Helen Davies, PH.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

John M. Daly, M.D.

Division of Surgical Oncology, the Department of Surgery and Microbiology, and the University of Pennsylvania School of Medicine and the Harrison Department of Surgical Research, Philadelphia, Pennsylvania

Administration of chemotherapy is limited by host toxicity, which is often manifested by severe enterocolitis. This study evaluated the effects of a liquid, elemental, chemically defined diet (ED) supplemented with 2% glutamine (Glu-ED) compared with a polypeptide diet (PPD) on the morbidity and mortality after methotrexate (MTX) administration. Fischer 344 rats (n=80) were fed either a regular rat chow diet (RD), a 2% glycine supplemented elemental diet (Gly-ED), a 2% glutamine-supplemented elemental diet (GLU-ED), and a glycine-supplemented polypeptide diet(Gly-PPD) for 7 days prior to administration of MTX (20 mg/kg, ip). After 72 hours, eight rats per group were killed; portal vein and vena cava blood, mesenteric lymph nodes (MLN), liver, small intestine, and cecum were sampled for bacterial culture. Remaining animals were followed to calculate survival.

One hundred percent of the Gly-PPD and 25% of the Glu-ED animals survived compared with 0% of the Gly-ED animals. Our data showed that ED resulted in an increased quantity of intestinal Gram-negative bacteria and diminished intestinal mucosal height and mucosal DNA/protein content. The polypeptide diet prevented intestinal mucosal atrophy, avoided MTX-induced enterocolitis and significantly improved animal survival compared with an elemental diet with or without glutamine supplementation. (Journal of Parenteral and Enteral Nutrition 15 :307-312, 1991)

Journal of Parenteral and Enteral Nutrition, Vol. 15, No. 3, 307-312 (1991)
DOI: 10.1177/0148607191015003307
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