STUDIES ON THE FATE OF THIABENDAZOLE (TBZ) IN MICE .3. EFFECT OF ORAL-ADMINISTRATION OF TBZ ON THE KIDNEY OF FEMALE MICE

Activities of alkaline phosphatate (ALP), leucine aminopeptidase (LAP) and γ-glutamyl transpeptidase (γ-GTP), which were all present at high concentration in the proximal tubules, were determined for the serum and homogenate from kidney and liver of mice to assess nephropathy induced after oral administration of thiabendazole (TBZ), which was suspended in olive oil or in 3% gum arabic to female mice at a dosage of 350, 700 and 1300 mg/kg/d for 5 or 10 d. Kidney tissue preparations were also examined by microscopy. The specific activities of both ALP and LAP in the liver increased after the repetitive administration of TBZ. Specific activities of ALP, LAP and γ-GTP in the kidney increased at a dose level of 350 mg/kg/d for 10 d, but they decreased at a dose level of either 700 and 1300 mg/kg/d for 10 d, or 1300 mg/kg/d for 5 d. Marked changes in kidney tissues were observed microscopically at a dose level of 1300 mg/kg/d. The brush border disappeared and the tubular lumen was dilated. These results indicate an induction of nephropathy by TBZ which is accompanied by changes in the proximal tubules of mice. © 1990, The Pharmaceutical Society of Japan. All rights reserved.