Journal of pediatric surgery · 2025
Vesicular nucleotide transporter inhibition via clodronate attenuates intestinal glucose transporter expression in short bowel syndrome rat model: A clear issue to nutritional adaptation.
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Nagano Ayaka, Tsuruno Yudai, Sugita Koshiro, Onishi Shun, Tabata Yumiko, Kedoin Chihiro, Murakami Masakazu, Yano Keisuke, Harumatsu Toshio, Kawano Takafumi, Hasuzawa Nao, Nomura Masatoshi, Kaji Tatsuru, Ieiri Satoshi
Аннотация
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.
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.