Intestinal toxicity induced by 5-fluorouracil in pigs: a new preclinical model.
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.


CONCLUSIONS
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.
Manzano
M
M
Strategic R&D Department, Abbott Nutrition International, Granada, Spain.
Bueno
P
P
Rueda
R
R
Ramirez-Tortosa
C L
CL
Prieto
P A
PA
Lopez-Pedrosa
J M
JM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D010084:Oxidation-Reduction; D013552:Swine