Ogasawara Y, Isoda S, Tanabe S
Department of Hygienic Chemistry, Meiji College of Pharmacy, Tokyo, Japan.
Toxicol Lett. 1998 Nov 12;99(3):191-8. doi: 10.1016/s0378-4274(98)00156-8.
The effects of trisulfide derivatives were studied on cytochrome P-450-dependent lipid peroxidation using rat liver microsomal systems. Cytochrome P-450-dependent lipid peroxidation was induced by carbon tetrachloride or tert-butylhydroperoxide and was evident by an increase in thiobarbituric acid-reactive substances (TBA-RS) and oxygen consumption. In these cytochrome P-450-dependent lipid peroxidation systems, pretreatment of microsome with trisulfide derivatives (cystine trisulfide and thiocyclam) significantly inhibited TBA-RS formation and oxygen consumption compared with disulfide or thiol analogs (cystine, nereistoxin, or cysteine). The labile sulfur contained in trisulfide disappeared during incubation with liver microsomes. In the CCl4-induced lipid peroxidation system, the cytochrome P-450 level and NAD(P)H-cytochrome P-450 reductase activity were significantly decreased by the addition of trisulfide derivatives. Therefore, in cytochrome P-450-dependent lipid peroxidation system, the potential effects of trisulfide appear to be mediated via enzyme inhibition. These results suggest that pretreatment of the trisulfide derivatives may affect the toxic function of exogenous xenobiotics or drugs, which are reduced by the liver enzyme cytochrome P-450 to radical species.
利用大鼠肝微粒体系统研究了三硫化物衍生物对细胞色素P-450依赖性脂质过氧化的影响。细胞色素P-450依赖性脂质过氧化由四氯化碳或叔丁基过氧化氢诱导，硫代巴比妥酸反应性物质（TBA-RS）增加和耗氧量增加证明其存在。在这些细胞色素P-450依赖性脂质过氧化系统中，与二硫化物或硫醇类似物（胱氨酸、沙蚕毒素或半胱氨酸）相比，用三硫化物衍生物（胱氨酸三硫化物和噻嗪酮）预处理微粒体可显著抑制TBA-RS的形成和耗氧量。三硫化物中含有的不稳定硫在与肝微粒体孵育期间消失。在CCl4诱导的脂质过氧化系统中，添加三硫化物衍生物可显著降低细胞色素P-450水平和NAD(P)H-细胞色素P-450还原酶活性。因此，在细胞色素P-450依赖性脂质过氧化系统中，三硫化物的潜在作用似乎是通过酶抑制介导的。这些结果表明，三硫化物衍生物的预处理可能会影响外源性异生物素或药物的毒性功能，这些物质会被肝细胞色素P-450还原为自由基。
