Monroy-Noyola A, Sogorb M A, Vilanova E
Laboratorio de Neuroprotección, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Universidad 1001, Chamilpa, C.P. 62210 Cuernavaca, México.
Toxicol Lett. 2007 Apr 25;170(2):157-64. doi: 10.1016/j.toxlet.2007.03.002. Epub 2007 Mar 12.
Calcium-dependent and EDTA-resistant hydrolyses of R and S isomers of O-hexyl O-2,5-dicholorophenyl phosphoramidate (HDCP) were observed in serum and subcellular fractions of liver, kidney and brain from hen, rat and rabbit. In serum, the Ca(2+)-dependent hydrolysis was much higher in rabbit than in other species. Liver showed a higher activity than kidney and brain. The S-HDCP isomer was hydrolysed to a higher extent than the other isomer. The fact that this stereospecificity favours the S-isomer is more clearly observed in rabbit serum, and in rat and rabbit liver particulate fractions. In such tissues and species, the EDTA-resistant hydrolysis was not stereospecific. Soluble fractions of rat brain and of hen liver, kidney and brain, showed a lower total activity but with a higher proportion of EDTA-resistant activity and a higher hydrolysis of the R-HDCP isomer. The Ca(2+)-dependent stereoselective biodegradation of S-HDCP is dominant in the most active tissues in rabbit and rat. It can therefore be concluded that S-HDCP would be biodegraded faster than R-HDCP. Furthermore, R-HDCP is the isomer that will remain at a higher proportion to be available for interaction with the target of neurotoxicity.
在母鸡、大鼠和兔子的血清以及肝脏、肾脏和大脑的亚细胞组分中，观察到了O-己基-O-2,5-二氯苯基氨基磷酸酯（HDCP）的R和S异构体的钙依赖性及乙二胺四乙酸（EDTA）抗性水解。在血清中，兔子的钙依赖性水解比其他物种高得多。肝脏的活性高于肾脏和大脑。S-HDCP异构体的水解程度高于另一种异构体。这种立体特异性有利于S异构体的现象在兔血清以及大鼠和兔子的肝脏微粒体组分中更为明显。在这些组织和物种中，EDTA抗性水解没有立体特异性。大鼠脑以及母鸡肝脏、肾脏和大脑的可溶性组分显示出较低的总活性，但EDTA抗性活性比例较高，且R-HDCP异构体的水解程度较高。在兔子和大鼠的活性最高的组织中，S-HDCP的钙依赖性立体选择性生物降解占主导。因此可以得出结论，S-HDCP的生物降解速度比R-HDCP快。此外，R-HDCP是将以更高比例留存从而可与神经毒性靶点相互作用的异构体。
