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Thiabendazole (TBZ) nephrotoxicity and recovery in ICR adult mice
Y Tada1, T Fujitani, M Yoneyama
1Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Abstract:
The nephrotoxicity and recovery following administration of thiabendazole (TBZ) were investigated in ICR adult mice. A single oral administration of TBZ (500-2000 mg/kg body wt.) caused a dose-dependent proximal tubular necrosis in the kidney and increase in serum urea nitrogen 24 h after dosing. These changes were marked in mice of high dose groups (1000 or 2000 mg TBZ/kg body wt.). The time course of changes on kidney of mice treated with 1000 or 2000 mg TBZ/kg body weight were examined at 1, 2, 3, 5, 7 or 10 days after dosing. Light microscopy showed necrosis of proximal convoluted tubules from 1 day after dosing. Tubular necrosis was extensive 2 or 3 days after dosing. Partial regeneration from tubular necrosis was seen 3 days after dosing, and substantial regeneration had occurred from 5 days after dosing. Thus, TBZ-induced renal injury was most severe at 2 or 3 days after dosing and was followed by regeneration. Electron microscopy showed swelling of mitochondria in the proximal tubular epithelium at 1 day after dosing. The pathological changes were correlated with the changes in urinalysis, serum urea nitrogen concentration and kidney weight.
Insights
Thiabendazole (TBZ) causes dose-dependent kidney damage, specifically proximal tubular necrosis, in mice. Renal injury peaks at 2-3 days post-dose, followed by significant tubular regeneration.
Area of Science:
- Toxicology
- Nephrology
- Pharmacology
Background:
- Thiabendazole (TBZ) is an anthelmintic drug.
- Understanding TBZ's renal effects is crucial for safe usage.
- Previous studies have not fully detailed TBZ-induced nephrotoxicity and recovery.
Purpose of the Study:
- To investigate the nephrotoxicity of thiabendazole (TBZ) in ICR adult mice.
- To characterize the time course of kidney injury and recovery following TBZ administration.
- To correlate pathological kidney changes with clinical and biochemical markers.
Main Methods:
- Adult ICR mice received single oral doses of TBZ (500-2000 mg/kg).
- Kidney tissues were examined using light and electron microscopy at various time points (1-10 days).
- Serum urea nitrogen, urinalysis, and kidney weight were measured.
Main Results:
- TBZ caused dose-dependent proximal tubular necrosis and increased serum urea nitrogen.
- Renal injury was most severe 2-3 days after high-dose TBZ administration.
- Tubular regeneration began by day 3 and was substantial by day 5; mitochondrial swelling observed.
Conclusions:
- TBZ induces significant, but reversible, nephrotoxicity in mice.
- The severity of TBZ-induced renal injury is dose-dependent.
- Kidney function and structure recover within 5-10 days post-exposure.
