Oishi S
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Arch Toxicol. 1990;64(2):143-7. doi: 10.1007/BF01974400.
Although it is well established that high dose administration of di(2-ethylhexyl) phthalate (DEHP) and its monoester metabolite (MEHP) induces severe testicular atrophy in rats, the mechanisms of this testicular injury is not clear. The present experiment was undertaken to examine the effects of DEHP and MEHP on mitochondrial functions of rat testis. DEHP and di-n-octyl phthalate (DOP), a DEHP isomer which causes less severe testicular injury, did not inhibit the state 3 oxygen consumption up to 0.65 mumole/ml in vitro. On the other hand, MEHP and mono-n-octyl phthalate (MOP), a metabolite of DOP, inhibited the state 3 oxygen consumption down to a concentration of 0.065 mumole/ml. Testicular mitochondrial respiratory functions of rats administered 2 g/kg DEHP were lower than those of control or DOP-treated rats. These differences were verified by characteristics of pharmacokinetic parameters and testicular concentrations of MEHP and MOP. It may be suggested that a possible mechanism of testicular atrophy induced by DEHP may be due to direct inhibition by MEHP (and partially DEHP) of the respiratory functions of Sertoli cell mitochondria in rat testis.
虽然已充分证实，高剂量施用邻苯二甲酸二（2-乙基己基）酯（DEHP）及其单酯代谢物（MEHP）会导致大鼠严重的睾丸萎缩，但其睾丸损伤机制尚不清楚。本实验旨在研究DEHP和MEHP对大鼠睾丸线粒体功能的影响。DEHP和邻苯二甲酸二正辛酯（DOP，一种导致睾丸损伤较轻的DEHP异构体）在体外高达0.65微摩尔/毫升的浓度下，并未抑制状态3耗氧量。另一方面，MEHP和DOP的代谢物单正辛酯（MOP）在浓度低至0.065微摩尔/毫升时，仍会抑制状态3耗氧量。给予2克/千克DEHP的大鼠的睾丸线粒体呼吸功能低于对照组或DOP处理组的大鼠。这些差异通过药代动力学参数特征以及MEHP和MOP的睾丸浓度得到证实。可以推测，DEHP诱导睾丸萎缩的可能机制可能是MEHP（以及部分DEHP）对大鼠睾丸支持细胞线粒体呼吸功能的直接抑制作用。
