Effect of fiber, protein source and time of feeding on methotrexate toxicity in rats

Several rat experiments were conducted to determine effects of fiber and alternate protein sources on methotrexate (MTX) toxicity associated with a casein-based semipurified diet. Additional experiments were conducted to determine the critical time of feeding in relation to toxicity development. Rats adapted to a casein-based semipurified diet developed severe anorexia and diarrhea on d 3 and 4 post-MTX dosing. Addition of amorphous cellulose to the semipurified casein-based diet slightly reduced toxicity symptoms. Additions of crystalline cellulose, hemicellulose and pectin did not lessen toxicity symptoms. Replacing casein with soybean concentrate totally alleviated the toxicity symptoms. Toxicity was lower when 25% of the protein normally supplied by casein was replaced with soybean concentrate, and no toxicity symptoms were present when 50% or more of the protein was provided by soybean concentrate. Replacing casein with whey isolate or hamburger had no effect on toxicity; replacing casein with egg albumen or corn gluten meal lessened toxicity symptoms but did not totally alleviate them. Feeding the casein-based diet only 1 d before and 1 d after MTX injection resulted in toxicity. However, feeding the same diet only after MTX injection did not cause toxicity. Results indicate that fiber sources have little effect on MTX toxicity, but replacing casein with soybean concentrate completely alleviates toxicity symptoms. Time of feeding affects subsequent development of toxicity.