O-Hexyl, O-2,5-dichlorophenyl phosphoramidate (HDCP) is a chiral compo
und that induces delayed neuropathy in hens. This compound is hydrolyz
ed by a phosphotriesterase known as HDCPase in hen and rat plasma, liv
er and brain. We studied the stereospecificity of HDCPase in hen tissu
es and in human and rabbit plasma employing a chromatographic method f
or analysis and quantification of HDCP stereoisomers. Hen and human pl
asma HDCPases were not stereospecific. However, rabbit plasma showed a
remarkable stereospecificity to S-(-)-HDCP. High levels of stereospec
ific HDCPase were found in the particulate fraction of hen liver, wher
e S-(-)-HDCP is hydrolyzed faster than R-(+)-HDCP. However, in hen bra
in the stereospecificity was found in the soluble fraction, where R-()-HDCP is hydrolyzed faster than S-(-)-HDCP. It is concluded that live
r particulate fraction must be the main tissue responsible for the HDC
P stereospecific biotransformation in hens. In an oral administration,
the steroisomer R-(+)-HDCP would survive after passing through the li
ver and would interact with acetylcholinesterase and neuropathy target
esterase in the nervous system. (C) 1998 Elsevier Science Ireland Ltd
. All rights reserved.