Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets
Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets
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DOI：
10.1007/s00204-004-0615-7
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发表时间：
2005-03-01
影响因子：
6.1
通讯作者：
Nakajima, T
中科院分区：
文献类型：
--
作者：
Ito, Y;Yokota, H;Nakajima, T
为了阐明邻苯二甲酸二（2-乙基己基）酯（DEHP）代谢的物种差异，我们在小鼠（CD-1）、大鼠（Sprague-Dawley）和绒猴（Callithrix jacchus）的几个器官（肝脏、肺、肾脏和小肠）中测量了四种DEHP代谢酶（脂肪酶、udp -葡萄糖醛基转移酶（UGT）、醇脱氢酶（ADH）和醛脱氢酶（ALDH））的活性。用DEHP生成邻苯二甲酸单（2-乙基己基）酯（MEHP）的速率来测定脂肪酶活性，不同物种之间的差异为27- 357倍；该活性在小鼠的小肠中最高，在狨猴的肺部最低。这可能是由于DEHP脂肪酶的Vmax/Km值在不同物种之间存在显著差异。肝微粒体中MEHP的UGT活性在小鼠中最高，其次是大鼠和狨猴。然而，与脂肪酶活性相比，这些差异只是微不足道的。ADH和ALDH活性在不同物种间也存在差异；前者在狨猴肝脏中的活性是大鼠或小鼠肝脏的1.6 ~ 3.9倍；后者在大鼠和狨猴中的活性高于小鼠（2-14倍）。这些结果与脂肪酶或UGT活性有很大不同。由于MEHP被认为是参与不同毒性过程的过氧化物酶体增殖体激活受体α的更有效的配体，因此从啮齿动物到人类的外推也可能考虑到MEHP形成能力的主要差异。
To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6-3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2-14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor alpha involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.