Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model

Abstract

BACKGROUND: The goal of this study was to develop an animal model of intestinal injury induced by 5-fluorouracil (5-FU) in pigs. METHODS: Six domestic pigs were used as control (healthy group) and another 6 malnourished pigs orally received 5-FU (treated group). After 4 weeks of treatment, pigs were sacrificed and jejunum, ileum and colon were isolated for histological, immunological and biochemical analyses. RESULTS: 5-FU caused a decrease in the intestinal mass. Disaccharidase, and phosphate alkaline activities, and glutathione redox cycle were disrupted by 5-FU. Histopathological alterations in the crypts and villous were greater in the small intestine than in the colon. 5-FU decreased the number of peripheral and intestinal leukocytes, promoting an increase in T-cytotoxic cells and a decrease in T-helper and B cells. CONCLUSION: This pig model of intestinal dysfunction closely mimics the common side effects of cancer chemotherapy in humans, and provides a useful tool for evaluating novel antimucotoxic agents.