[Effect of thiabendazole (TBZ) on glutathione (GSH) and GSH related enzymes in mice liver].
The present study examines the effects of thiabendazole (TBZ), its metabolites, 5-hydroxythiabendazole (5-OH TBZ) and 2-acetylbenzimidazole (ABI), and structural related compounds, thiazoles and thioamides on glutathione (GSH) concentration and GSH-related enzymes in the livers of ICR 11 week-old female mice. GSH concentration in liver and kidney of mice given orally TBZ 0.65 mol/kg (TBZ group) increased significantly compared with control mice from 24 h to 48 h after administration of TBZ. Even in mice to which TBZ at 0.175 mol/kg was administered in combination with L-buthionine sulfoximine (BSO) 4 mmol/kg (i.p.) (BSO-TBZ group), kidney GSH showed significant increase compared with BSO-control mice 48 h after the administration of TBZ. gamma-Glutamylcysteine synthetase (gamma-GCS) activity in the livers of the TBZ group markedly increased at 48 h and that of BSO-TBZ group increased from 24 h to 48 h. gamma-GCS in mice liver is thus enhanced by TBZ regardless of BSO administration. Hepatic glutathione peroxidase activity of the TBZ group did not change in response to cumene hydroperoxide assubstrate. That of BSO-treated mice decreased by TBZ-coadministration and significant differences was noted between BSO-control and BSO-TBZ group from 1 h to 48 h later. Hepatic glutathione S-transferase (GST) activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was significantly elevated 24 h after administrations of TBZ in TBZ and BSO-TBZ groups. GST activity toward 1,2-epoxy-3-(p-nitrophenoxy) propane of TBZ group increased from 0.5 h to 24 h. Hepatic GST activity toward DCNB and 1-chloro-2,4-dinitrobenzene did not change by administration of 0.65 mol/kg 5-OH TBZ or ABI but increased by administrations of 0.33 mol/kg of thiazole, 4-methylthiazole, 4,5-dimethylthiazole or 2,4-dimethylthiazole. Increase in GSH concentration and GST activity in mice liver by TBZ administration may be considered to provide protection from TBZ or its active metabolites.
Toda
C
C
Faculty of Pharmacy Meijo University, Nagoya, Japan.
Yasui
T
T
Hashizume
K
K
Nagano
H
H
D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D013827:Thiabendazole / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology
D000969:Antinematodal Agents; D013844:Thiazoles; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D013827:Thiabendazole