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Evaluation of damaged small intestine of mouse following methotrexate administration
M Nakamaru1, Y Masubuchi, S Narimatsu
1Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Purpose:
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.
Insights
Methotrexate (MTX) damages the small intestine, increasing permeability. This study shows MTX disrupts the paracellular barrier, leading to greater marker passage and potential malabsorption.
Area of Science:
- Gastroenterology
- Pharmacology
- Cell Biology
Background:
- Methotrexate (MTX) treatment is known to cause small intestine damage, leading to malabsorption and diarrhea.
- MTX diminishes both active and passive transport capacities in the small intestine.
Purpose of the Study:
- To evaluate small intestine damage induced by MTX in mice.
- To examine the paracellular pathway permeability of the small intestinal epithelium following MTX administration.
Main Methods:
- Male ddY mice received daily oral MTX for 1-6 days.
- Permeability was assessed using nonabsorbable markers: phenol red (PR) and fluorescein isothiocyanate (FITC) dextrans.
- Everted intestinal segments were utilized for permeability measurements.
Main Results:
- A significant increase in PR and FITC dextran permeation was observed.
- Increased permeation correlated with changes in mouse body weight.
- Alterations in small intestine wet weight and epithelial chemical composition were noted.
Conclusions:
- MTX treatment impairs the paracellular barrier function of the small intestinal epithelium.
- This impairment results in increased paracellular pathway permeation of nonabsorbable markers.
- The methodology provides a valuable approach for assessing intestinal damage and malabsorption.