Evaluation of damaged small intestine of mouse following methotrexate administration.
OBJECTIVE
Methotrexate (MTX) treatment causes damage to the small intestine, resulting in malabsorption and diarrhea. The active and passive transport capacities of the small intestine are decreased by the treatment. The purpose of this study was to evaluate the damage to the small intestine of mice caused by MTX administration by examining the permeability of the paracellular pathway of the small intestinal epithelium.


METHODS
MTX was administered orally to male ddY mice once daily for 1-6 days. The permeability of the small intestine to the nonabsorbable markers phenol red (PR) and fluorescein isothiocyanate (FITC) dextrans was examined using everted segments of the intestine.


RESULTS
PR and FITC dextran permeation through the small intestine increased significantly in parallel with changes in body weight of the mice, wet weight of the small intestine and chemical composition of the small intestinal epithelium.


CONCLUSIONS
In addition to changes in permeation through the transcellular pathway reported previously, this study revealed that MTX treatment disorders the paracellular barrier function of the small intestinal epithelium, resulting in increased permeation of nonabsorbable markers via the paracellular pathway of the small intestinal mucosa. The present approach to the examination of the barrier function of the intestinal epithelium could be of great use in evaluating the damage to the small intestine and malabsorption.
Nakamaru
M
M
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Masubuchi
Y
Y
Narimatsu
S
S
Awazu
S
S
Horie
T
T
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003911:Dextrans / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D051379:Mice; D010539:Permeability / Q000187:drug effects
D000925:Anticoagulants; D000964:Antimetabolites, Antineoplastic; D003911:Dextrans; D008727:Methotrexate