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https://hdl.handle.net/2142/19036
Description
Title
Effect of diet on methotrexate toxicity
Author(s)
Funk, Martha A.
Issue Date
1990
Doctoral Committee Chair(s)
Baker, David H.
Department of Study
Division of Nutritional Sciences
Discipline
Human Nutrition
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Toxicology
Nutrition
Language
eng
Abstract
Experiments were conducted to examine effects of different diets and regimens on gastrointestinal toxicity induced by methotrexate (MTX) in rats. Toxicity was determined by severity of anorexia and incidence of diarrhea on d 3 and 4 following an intraperitoneal injection of 20 mg MTX per kg body weight. Rats adapted to a casein-based semipurified diet for 14 d developed severe toxicity post-MTX dosing. Toxicity was not present in rats fed a complex diet containing corn and soybean meal before and after MTX injection. Toxicity occurred when the semipurified diet was fed only 1 d prior to and 1 d after MTX injection. Feeding the semipurified diet only after MTX injection did not result in toxicity. The complex diet had to be fed more than 3 d prior to MTX dosing in order to provide its protective benefits. Addition of amorphous cellulose to the semipurified casein-based diet slightly reduced toxicity. Additions of crystalline cellulose, hemicellulose, and pectin did not lessen toxicity. Replacing casein with whey isolate or hamburger had no effect on toxicity while replacing casein with egg albumin or corn gluten meal lessened toxicity signs but did not totally alleviate them. Soy products including soybean meal, soy concentrate, soy isolate and soy fiber were tested for their effect on MTX toxicity when included in a semipurified diet. Soybean meal and soy concentrate prevented anorexia and diarrhea when they replaced casein as the protein source. Soy concentrate alleviated toxicity when it supplied 50% of the protein with the remainder being provided by casein. Toxicity decreased with inclusion of soy isolate and soy fiber, but performance did not equal that obtained with soybean meal or soy concentrate. Histological examination of small intestine of MTX-injected animals revealed that soy concentrate and soy isolate prevented necrosis that was observed in animals consuming the casein-based semipurified diet. Methotrexate levels in plasma were similar for animals consuming semipurified diets where the protein was supplied by casein, soy concentrate or soy isolate. Methotrexate caused a depression in white blood cell count in animals consuming the complex diet or the semipurified diet containing casein, soy isolate or soy concentrate.
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