Because CPO is approximately 1,000 times more potent than CPF as an AChE inhibitor (Das and Barone 1999), we first examined a concentration of 30 nM and found a smaller effect on AChE-R expression, intermediate between control levels and the higher values evoked by 30 [micro]M CPF or DZN.
Similarly, for AChE-S (Figure 4B), DZN evoked significant increases in expression at either 0.
Second, and even more critically, whereas CPF was as effective and DZN more effective in inducing AChE-S as it was for AChE-R, CPO failed to evoke any AChE-S increase whatsoever.
Although the majority of work on the developmental neurotoxicity of OPs has centered around the effects of CPF (Pope 1999; Slotkin 1999, 2004, 2005), recent evidence implicates a similar spectrum of actions for DZN (Abu-Qare and Abou-Donia 2001; Aluigi et al.
Our finding that CPF and DZN induce both AChE isoforms while CPO induces only the AChE-R variant is in agreement with findings from Alzheimer disease therapeutics (Darreh-Shori et al.
Conversely, serum PXN and DZN activities are influenced by both PON1 protein concentrations and Q192R genotype.
Because the specific activities of both PXN and DZN differ across the Q192R genotypes, serum PXN and DZN activity will change with total PON1 protein concentration and relative amounts of the type Q and R isoenzymes in a sample.
2] Nonstandard abbreviations: PON1, paraoxonase 1; OP, organophosphate; AE, arylesterase; PXN, paraoxonase; DZN, diazoxonase; A, absorbance.
The dosing paradigms were chosen to achieve a toxicodynamic match between DZN and PRT (Slotkin et al.
DZN produced a significant overall reduction in body weight at either 0.
0001) and between DZN and PRT [treatment x (DZN vs.
Accordingly, we separated the results for DZN and PRT for each age point and then reexamined the treatment effects.