Nakagawa Y, Moore G A
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Life Sci. 1995;57(15):1433-40. doi: 10.1016/0024-3205(95)02106-s.
The cytotoxic effects of ortho-phenylphenol (OPP), imazalil (IMZ) and thiabendazole (TBZ) on isolated rat hepatocytes were investigated. Addition of IMZ and OPP to hepatocyte suspensions at a concentration of 0.75 mM resulted in acute cell death, accompanied by depletion of intracellular levels of glutathione and protein thiols. Both compounds rapidly depleted cellular ATP which consistently preceded the cell death. In addition, the cell death caused by IMZ was accompanied by the accumulation of intracellular malondialdehyde, indicating initiation of lipid peroxidation. During a 3-hr incubation period, TBZ did not affect these parameters. In mitochondria isolated from rat liver, IMZ and OPP impaired respiration related to oxidative phosphorylation. Based on these results, the order of toxic potency is IMZ > OPP > TBZ.
研究了邻苯基苯酚（OPP）、抑霉唑（IMZ）和噻苯达唑（TBZ）对分离的大鼠肝细胞的细胞毒性作用。以0.75 mM的浓度将IMZ和OPP添加到肝细胞悬液中会导致急性细胞死亡，同时伴随着细胞内谷胱甘肽和蛋白质巯基水平的耗尽。这两种化合物均迅速耗尽细胞内ATP，而细胞内ATP的耗尽始终先于细胞死亡。此外，IMZ引起的细胞死亡伴随着细胞内丙二醛的积累，表明脂质过氧化开始。在3小时的孵育期内，TBZ未影响这些参数。在从大鼠肝脏分离的线粒体中，IMZ和OPP损害了与氧化磷酸化相关的呼吸作用。基于这些结果，毒性强度顺序为IMZ > OPP > TBZ。
