We repeated the phenotyping as described by Richter and Furlong (20), plotting activity levels of PXN and DZN and the PXN/DZN ratio (Fig.
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.
In animal models, developmental neurotoxicity results from either CPF or DZN at doses that do not elicit any signs of systemic intoxication and even at exposures below the threshold for inhibition of acetylcholinesterase (AChE), which is often considered to be the primary target for OPs (Slotkin 1999, 2004, 2005; Slotkin et al.
In contrast, CPF and DZN both elicit adverse effects on brain development at much lower exposures, and the adverse effects involve the native compounds and not their hepatically produced oxon metabolites, which are the actual agents that cause irreversible AChE inhibition (Slotkin 1999, 2004, 2005; Slotkin et al.
In this model, we compared the effects of CPF and DZN to that of CPF oxon (CPO), which is three orders of magnitude more potent toward inhibition of AChE than the parent compound, CPF (Das and Barone 1999).
5 S murine NGF (Invitrogen), along with CPF, CPO, or DZN (Chem Service, West Chester, PA).