Effect of enteral formulas on methotrexate toxicity.

Type of diet influences toxic effects of the chemotherapeutic drug methotrexate (MTX) on the gastrointestinal tract (GI) tract. In this study, commercial enteral products containing various protein types were tested to determine whether they exacerbated or alleviated MTX-induced GI toxicity in a non-tumor-bearing animal model receiving a single injection of MTX (20 mg/kg). Five enteral products containing casein or soy isolate in various forms as the primary source of protein were used. One casein-based product also contained soy fiber. These diets were compared with a soy concentrate-based diet and a casein-based diet prepared by the authors. Each diet was fed to 10 rats for seven days before injection and seven days after injection. In animals fed soy isolate or hydrolyzed or intact casein without added soy fiber, food intake was < 30% of pre-MTX injection levels on Days 3 and 4 after injection. These animals also lost weight and had diarrhea. Rats consuming the casein-based diet with fiber experienced some protection against MTX toxicity. Food intake only dropped to 63% of preinjection levels, weight was maintained, and no diarrhea occurred. Rats fed soy concentrate maintained food intake above 90% of preinjection levels, which was greater than all other groups at Day 3 and those receiving hydrolyzed or intact casein without fiber on Day 4 (p < 0.05). Weight gain in the soy concentrate group was also different from that in groups fed hydrolyzed or intact casein without fiber (p < 0.05). Rats consuming soy concentrate had no diarrhea. A second experiment was conducted to evaluate histological damage to the intestine when these diets were fed to animals injected with MTX. This experiment was conducted in the same manner as the first experiment, except animals were sacrificed on Day 3 after injection and samples were obtained from the jejunum. Crypt necrosis occurred in all groups except those consuming the soy concentrate diet or the enteral product containing soy fiber. Results indicate that soy concentrate is superior in alleviating MTX toxicity compared with commercial enteral products.

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 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)

The effect of fiber source in enteral products on fecal weight, mineral balance, and growth rate in rats.

The effect of two fiber systems in enteral formulas on fecal output, mineral balance, weight gain, and cecal short-chain fatty acid production was studied in rats. Enteral products tested had either no fiber; soy fiber (3.4 g of total dietary fiber/8 fluid oz); a fiber blend containing 75% oat fiber, 17.5% gum arabic, and 7.5% carboxymethylcellulose (3.4 g of total dietary fiber/8 fluid oz); or the same blend at 4 g of total dietary fiber/8 fluid oz. Food, feces, and urine were analyzed for nitrogen, calcium, magnesium, iron, and zinc. Cecal contents were analyzed for short-chain fatty acids. Weight gain, intake, food efficiency, and nitrogen balance were unaffected by fiber source. Fecal weight was increased by the fiber blend (p < .05). Calcium and magnesium balances were similar for all groups fed fiber-containing products but were lower for the fiber-free group (p < .05). Iron balance was significantly lower for rats fed the fiber blend at 4 g/8 fluid oz as compared with the other treatment groups (p < .05). Cecal acetate, propionate, and total short-chain fatty acid concentrations for rats fed the soy-fiber diet were significantly higher than for the other three diets (p < .05). Rats fed the fiber blend at the higher level had a significantly higher percentage of butyrate production than rats fed the other three diets (p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)