Hayashi Y, Toyoda K, Imazawa T, Sato H, Okamiya H, Kurokawa Y, Takahashi J, Mogami-Nishimaki T, Hayakawa S
Biological Safety Research Center, National Institute of Hygienic Sciences, Tokyo, Japan.
Exp Toxicol Pathol. 1994 Jul;46(2):127-32. doi: 10.1016/S0940-2993(11)80041-2.
Three-week oral administration of 4-(decahydro-6-methyl-3-oxo-cyclopenta(f)quinoline-7-yl)valeric acid (32-1328) in the diet supplemented at concentrations of 0.1% or 0.3% was associated with hepatomegaly and hypotriglyceridemia in male F344 rats. Electron microscopic examination of the liver revealed a remarkable increase of peroxisomes in hepatocytes both in number and size. Biochemically, there were increased activities of peroxisomal marker enzymes including the heat-labile enoyl-CoA hydratase and catalase while the mitochondrial enoyl-CoA hydratase activity was unchanged after feeding of 32-1328. These findings indicate that 32-1328 can exert peroxisome-proliferating activity to rat liver in a manner similar to typical peroxisome proliferators such as clofibrate or di(2-ethylhexyl)phthalate.
在雄性F344大鼠的饮食中添加浓度为0.1%或0.3%的4-(十氢-6-甲基-3-氧代-环戊并[f]喹啉-7-基)戊酸(32-1328)进行为期三周的口服给药,与肝肿大和低甘油三酯血症有关。肝脏的电子显微镜检查显示,肝细胞中过氧化物酶体的数量和大小均显著增加。生化方面,包括热不稳定烯酰辅酶A水合酶和过氧化氢酶在内的过氧化物酶体标记酶的活性增加,而喂食32-1328后线粒体烯酰辅酶A水合酶的活性未发生变化。这些发现表明,32-1328能够以类似于典型过氧化物酶体增殖剂如氯贝丁酯或邻苯二甲酸二(2-乙基己基)酯的方式对大鼠肝脏发挥过氧化物酶体增殖活性。