Effects of thiabendazole (TBZ) on mitochondrial function in renal cortex of ICR mice.
The effects of thiabendazole (TBZ) on mitochondrial function of the renal cortex were investigated in ICR mice. Mice were given 1000 or 2000 mg TBZ/kg body weight by gavage and mitochondria were isolated from the renal cortex for the measurement of respiratory rates. The state 3 and DNP-uncoupled respiratory rates of renal cortical mitochondria were dose-dependently depressed at 6 hours after dosing. The depression of these respiratory rates of renal cortical mitochondria was more marked at 16 hours after dosing. There was no depression in these respiratory rates of renal cortical mitochondria at 3 hours after dosing, although renal cortical concentrations of TBZ were higher than those at 6 or 16 hours after dosing. Histochemical examination revealed that NAD-linked isocitrate dehydrogenase, a marker enzyme of mitochondria, was inhibited in renal cortical tubules at 16 hours after dosing of 1000 or 2000 mg TBZ/kg body weight. Furthermore, renal cortical ATP level was significantly decreased at 16 hours after dosing of 1000 or 2000 mg TBZ/kg body weight. The results indicate that administration of TBZ caused mitochondrial dysfunction in renal cortical tubules of mice.
Fujitani
T
T
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Tada
Y
Y
Yoneyama
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000969:Antinematodal Agents / Q000633:toxicity*; D019069:Cell Respiration / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007521:Isocitrate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D013827:Thiabendazole / Q000633:toxicity*
D000969:Antinematodal Agents; D000255:Adenosine Triphosphate; D007521:Isocitrate Dehydrogenase; D013827:Thiabendazole