|
The purpose of this study was to investigate a role of cytochrome P_(450), for the toxicity of the phosalone in in vitro and in vivo bioactivation systems. The bimolecular inhibition rate constants(k_i) of the phosalone to acetylcholinesterase(AChE) and butyrylcholinesterase(BuChE) were approximately 10²M^(-1)min^(-1), respectively, which meant a poor inhibitor. The potency of the phosalone as an inhibitor of AChE and BuChE was increased about 300 and 40 fold, respectively, when the inhibitor and the ChE were incubated with microsomes fortified with NADPH compared with microsome alone. Piperonyl butoxide(PB) addition to these coupled systems greatly reduced the inhibition of both target enzymes by blocking a bioactivation process. The I_(50), value of the Phosalone alone for rat brain AChE was 170 ㎎/㎏. When PB was pretreated, that value was altered to 42.5 ㎎/㎏. PB pretreatment synergized the inhibition of brain AChE with four times. Rat blood erythrocyte AChE and plasma BuChE were similarly inhibited in vivo by the phosalone and PB pretreatment didn´t affect significantly the pattern of the inhibition. The in vivo studies showed different results in the role of cytochrome P_(450) from those of the in vitro studies.
|