Tada Y, Fujitani T, Yoneyama M
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Toxicology. 1994 Nov-Dec;94(1-3):41-55. doi: 10.1016/0300-483x(94)90027-2.
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.
在ICR成年小鼠中研究了噻苯达唑（TBZ）给药后的肾毒性及恢复情况。单次口服TBZ（500 - 2000毫克/千克体重）可导致肾脏出现剂量依赖性近端肾小管坏死，并在给药后24小时使血清尿素氮升高。这些变化在高剂量组（1000或2000毫克TBZ/千克体重）小鼠中较为明显。对接受1000或2000毫克TBZ/千克体重治疗的小鼠，在给药后1、2、3、5、7或10天检查其肾脏的变化过程。光学显微镜检查显示，给药后1天近端曲管出现坏死。给药后2或3天肾小管坏死广泛。给药后3天可见肾小管坏死部分再生，给药后5天出现大量再生。因此，TBZ诱导的肾损伤在给药后2或3天最为严重，随后出现再生。电子显微镜检查显示，给药后1天近端肾小管上皮细胞线粒体肿胀。病理变化与尿液分析、血清尿素氮浓度及肾脏重量的变化相关。
