Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

Abstract

Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo), and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets) for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

Effect of minimal enteral feeding on recovery in a methotrexate-induced gastrointestinal mucositis rat model

“…From day 5 till day 10, all rats were in their regular Plexiglas cages unattached from the swivels. Daily food intake and body weight were measured, and diarrhea, pica (= ingestion of non-food substances as sign of emesis [ 20 , 21 ]), and illness (bad fur, red nose, or decreased activity) were scored as yes/no. Every 2 days, the severity of mucositis was objectified by measuring plasma citrulline levels in blood samples from the tail tip (70 μl).…”

Animal models of chemotherapy-induced mucositis: translational relevance and challenges

“…IL-1β, IL-6, TNF-α, INF-γ), may affect food intake and energy expenditure leading to cancer cachexia (16). However, implanted tumors in rodents often comprise a greater fraction of total body weight, compared with humans, resulting in pronounced effects on whole body and GIT metabolism (15). This aspect complicates translation of CIM results in tumor-bearing rodent models and may explain some discrepancies between animal and human studies in studies of nutrition, chemotherapy and tumor growth (16,192).…”

Alterations in the small intestinal wall and motor function after repeated cisplatin in rat

“…Ki-67 is widely used as a cell proliferation marker. 34 Whereas some antineoplastic drugs, such as methotrexate, do not affect this early proliferation marker in the mucosa, 35 cisplatin decreased proliferating cells in the few hours after its administration. 32,36 However, we did not detect any significant change in this parameter, suggesting that mucosal proliferation was recovered 1 week after the last cisplatin administration.…”