EFFECT OF DIETS ON 5-FLUOROURACIL AND CYCLOPHOSPHAMIDE TOXICITY

Feeding rats a semipurified diet containing casein as a protein source results in severe gastrointestinal (GI) toxicity when the chemotherap eutic drug methotrexate (MTX) is given. However, when soy concentrate protein is used in place of casein, rats are completely protected from toxicity. The purpose of this study was to determine whether soy prot ein was also protective against two other chemotherapeutic agents, 5-f luorouracil (5-FU) and cyclophosphamide (CY), which are routinely used in a multidrug regimen with MTX in a clinical setting. Three diets we re tested; they consisted of a control complex diet (rat chow) and two semipurified diets containing casein or soy concentrate as the protei n fraction given to non-tumor-bearing rats receiving a single injectio n of 5-PU or CY at three different levels (Experiment I: 5-FU: 100, 26 0, and 420 mg/kg; Experiment II: CY: 120, 180, and 240 mg/kg). Each di et was fed to seven rats for seven days before injection and seven day s after injection. Food intake decreased at Day 3 in all groups receiv ing 5-FU (35-90% reduction from preinjection level), with the greatest decrease associated with the group receiving the highest drug level. Animals fed the control diet ate consistently less than animals fed th e other two diets regardless of the drug level. Intake was not signifi cantly different between the casein and soy concentrate groups at any drug level. Animals gained weight on the low-dose treatment regardless of diets. At 260 and 420 mg/kg 5-FU, all diet groups lost weight, but the difference was significant only between the control and the two o ther diets (p < 0.05). Diarrhea was absent in the casein diet groups, regardless of drug dose, and present in the other diet groups. Food in take decreased on Day I for all groups receiving CY; At any dose, the control diet group maintained a greater intake on Day 1 than the other two diet groups. The difference in intake was significant between the control and the two other diet groups at low dose, between the contro l and the casein diet groups at 180 mg/kg, and between the control and the soy concentrate diet groups at high dose (p < 0.05). Ah animals l ost weight regardless of diet and drug dose. A third experiment was co nducted to evaluate histological damage to the intestine when these th ree diets were fed to animals injected with 420 mg/kg 5-FU. This exper iment was conducted in the same manner as Experiment I, except animals were sacrificed on Day 3 after injection to remove jejunal samples. C rypt necrosis and debris occurred in all groups receiving 5-FU. Villus height was decreased in all groups, with a less reduction in the case in diet group, and the difference was significant with the 2 other die t groups (p < 0.05). Results indicate that none of the three diets pro moted significant protection against 5-FU- or CY-induced toxicity.