Vesicular nucleotide transporter inhibition via clodronate attenuates intestinal glucose transporter expression in short bowel syndrome rat model: A clear issue to nutritional adaptation.

BACKGROUND

Short bowel syndrome (SBS) is a condition resulting from extensive intestinal resection that requires total parenteral nutrition (TPN). Clodronate, a vesicular nucleotide transporter inhibitor, shows therapeutic potential for intestinal failure-associated liver disease; however, its effects on intestinal adaptation remain unexplored.

METHOD: Sprague-Dawley rats underwent 90 % small bowel resection and were randomized into three groups (n = 8 each): SBS/TPN (Control), SBS/TPN with low-dose clodronate (Low, 20 mg/kg/day), and SBS/TPN with high-dose clodronate (High, 60 mg/kg/day). Seven days after TPN administration, the intestinal morphology, crypt cell proliferation rate, sugar transporter expression, serum GLP-2 levels, and GLP-2 receptor expression were analyzed.

RESULTS

No significant differences were observed among the groups in intestinal morphology, including jejunal and ileal villus height, crypt depth, or absorptive area. The jejunal SGLT1 expression was significantly suppressed in a dose-dependent manner (Control: 0.58 ± 0.37, Low: 0.28 ± 0.13, High: 0.13 ± 0.08, p < 0.01), with significant differences between the Control and Low groups (p < 0.05) and between the Control and High groups (p < 0.01). Similarly, the jejunal GLUT2 expression decreased in a dose-dependent manner (Control: 0.59 ± 0.32; Low: 0.48 ± 0.27; High: 0.22 ± 0.12, p < 0.05). Serum GLP-2 levels were not significantly different among the 3 groups. There was no significant difference in the GLP-2 receptor expression between the Control and clodronate groups.

CONCLUSION

Clodronate may not have a positive effect on intestinal adaptation and could be inappropriate for the acute-phase SBS patients. Further research should focus on GLP-2 combination therapy, optimal timing, and dose adjustment to preserve intestinal function while maintaining hepatoprotective effects.

TYPE OF STUDY: Experimental research.