Chevreau N, Wang Y, Funk-Archuleta M
Foods and Nutrition Division, University of Utah, Salt Lake City 84112, USA.
Nutr Cancer. 1995;23(2):205-20. doi: 10.1080/01635589509514375.
Feeding rats a semipurified diet containing casein as a protein source results in severe gastrointestinal (GI) toxicity when the chemotherapeutic 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 protein was also protective against two other chemotherapeutic agents, 5-fluorouracil (5-FU) and cyclophosphamide (CY), which are routinely used in a multidrug regimen with MTX in a clinical setting. Three diets were tested; they consisted of a control complex diet (rat chow) and two semipurified diets containing casein or soy concentrate as the protein fraction given to non-tumor-bearing rats receiving a single injection of 5-FU or CY at three different levels (Experiment I: 5-FU: 100, 260, and 420 mg/kg; Experiment II: CY: 120, 180, and 240 mg/kg). Each diet was fed to seven rats for seven days before injection and seven days after injection. Food intake decreased at Day 3 in all groups receiving 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 the other two diets regardless of the drug level. Intake was not significantly 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 other diets (p < 0.05). Diarrhea was absent in the casein diet groups, regardless of drug dose, and present in the other diet groups. Food intake decreased on Day 1 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 control 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). All animals lost weight regardless of diet and drug dose. A third experiment was conducted to evaluate histological damage to the intestine when these three diets were fed to animals injected with 420 mg/kg 5-FU.(ABSTRACT TRUNCATED AT 250 WORDS)
给大鼠喂食以酪蛋白作为蛋白质来源的半纯化饮食，同时给予化疗药物甲氨蝶呤（MTX）时，会导致严重的胃肠道（GI）毒性。然而，当用大豆浓缩蛋白替代酪蛋白时，大鼠可完全免受毒性影响。本研究的目的是确定大豆蛋白对另外两种化疗药物5-氟尿嘧啶（5-FU）和环磷酰胺（CY）是否也有保护作用，这两种药物在临床环境中常与MTX联合用于多药治疗方案。测试了三种饮食；它们包括一种对照复合饮食（大鼠饲料）和两种半纯化饮食，其中分别含有酪蛋白或大豆浓缩物作为蛋白质成分，给予接受单次注射三种不同剂量（实验I：5-FU：100、260和420 mg/kg；实验II：CY：120、180和240 mg/kg）的5-FU或CY的无肿瘤大鼠。在注射前7天和注射后7天，每种饮食喂给7只大鼠。接受5-FU的所有组在第3天食物摄入量均下降（比注射前水平降低35 - 90%），其中药物剂量最高的组下降幅度最大。无论药物剂量如何，喂食对照饮食的动物始终比喂食其他两种饮食的动物吃得少。在任何药物剂量下，酪蛋白组和大豆浓缩物组之间的摄入量没有显著差异。无论饮食如何，低剂量治疗的动物体重增加。在5-FU剂量为260和420 mg/kg时，所有饮食组体重均下降，但仅对照饮食组与其他两种饮食组之间差异显著（p < 0.05）。无论药物剂量如何，酪蛋白饮食组均未出现腹泻，而其他饮食组出现腹泻。接受CY的所有组在第1天食物摄入量下降。在任何剂量下，对照饮食组在第1天的摄入量均高于其他两个饮食组。低剂量时，对照饮食组与其他两个饮食组之间的摄入量差异显著；在180 mg/kg时，对照饮食组与酪蛋白饮食组之间差异显著；高剂量时，对照饮食组与大豆浓缩物饮食组之间差异显著（p < 0.05）。无论饮食和药物剂量如何，所有动物体重均下降。进行了第三个实验，以评估当给注射420 mg/kg 5-FU的动物喂食这三种饮食时肠道组织学损伤情况。（摘要截断于250字）
