Favorable inhibitory effect of clodronate on hepatic steatosis in short bowel syndrome model rats
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In brief
In brief
Preclinical study demonstrates that high-dose clodronate, a VNUT inhibitor, reduces hepatic steatosis and inflammation in a rat model of short bowel syndrome receiving total parenteral nutrition. Findings suggest potential therapeutic application for preventing intestinal-failure-associated liver disease in SBS patients.
- High-dose clodronate (60 mg/kg twice weekly) reduced hepatic steatosis in rat SBS model receiving TPN compared to controls.
- Clodronate suppressed IL-6 and Nlrp3 inflammatory markers in liver tissue, suggesting anti-inflammatory mechanism in IFALD.
- VNUT inhibition may offer therapeutic approach for intestinal-failure-associated liver disease in short bowel syndrome patients.
- Effect was dose-dependent; high-dose clodronate showed histologic improvement while low-dose (20 mg/kg) did not differ from control.
- Lipid metabolism gene expression unchanged, suggesting clodronate acts via inflammation reduction rather than direct metabolic modulation.
Written by the GCMD Library team from the article.
Abstract
Purpose
This study investigated the anti-inflammatory effect of clodronate, a vesicular nucleotide transporter (VNUT) inhibitor, on intestinal-failure-associated liver disease (IFALD) in a rat model of short bowel syndrome (SBS).
Methods
The rats underwent jugular vein catheterization for continuous total parenteral nutrition (TPN) and 90% small bowel resection. The animals were divided into the following groups: TPN/SBS (Control group), TPN/SBS/intravenous administration of low-dose clodronate (20 mg/kg twice per week; Low group), or TPN/SBS/intravenous administration of high-dose clodronate (60 mg/kg twice per week; High group). On day 7, the rats were euthanized. Hepatic steatosis and hepatocellular injury were also assessed.
Results
Hepatic steatosis and lobular inflammation in the liver were observed in all groups. The High group showed histologically reduced hepatic steatosis compared with the Control group. IL-6 and Nlrp3 expression in the High group was significantly suppressed compared to that in the Control group. The expression of other inflammatory cytokines tended to be lower in the High dose group than in the control group. The lipid metabolism gene expression in the liver specimens showed no significant differences among the groups.
Conclusion
The high-dose administration of clodronate may, therefore, inhibit hepatic steatosis and inflammation associated with IFALD in patients with SBS.