In vitro and in vivo characterization of the contribution of hepatic and serum A-esterases and carboxylesterases to detoxication of organophosphate oxons in the juvenile and adult rat, Rattus norvegicus

The present study was designed to investigate the in vitro and in vivo contribution of hepatic and serum carboxylesterases (CaE) and A-esterases (AEST) to their respective stoichiometric and catalytic detoxication of organophosphorus insecticide oxons, [paraoxon (PO) and chlorpyrifos-oxon (CPO)], and the resultant protection of brain acetylcholinesterase (AChE). Initially, the development of the AEST was examined in Sprague-Dawley rats of several ages, using both direct and indirect quantitation methods. Hepatic and serum AEST increased with age in both sexes, and activities were detectable at postnatal (PND) day 1, using both high and low substrate concentrations. Secondly, the protective effect of CaE and AEST for brain ACNE was examined during in vitro exposures to PO and CPO. Protection was defined as a decrease in the anticholinesterase potency of a given concentration of oxon as a result of interaction with enzymes. Bovine brain AChE I₅₀'s for CPO and PO increased significantly when either hepatic and serum CaE or AEST were functional, indicating in vitro AChE protection by these two esterases. CaE was effective in AChE protection against both PO and CPO, whereas AEST was more effective against CPO. Thirdly, the protective effect of hepatic and serum CaE and AEST during in vivo exposures to CPO or PO, following exposure to the specific CaE inhibitor, bis-(4-nitrophenyl) phenylphosphonate (BNPP), were also investigated. In vivo exposures to the CaE inhibitor, BNPP, followed by exposure to CPO or PO resulted in significant reduction in rat brain and serum AChE activities. Brain AChE specific activities in CaE-inhibited rats (AEST active) were significantly lower than control activities. Generally, when CaE were not inhibited (CaE, AEST active), brain AChE activities were at or near control levels following CPO or PO exposures. In summary, both in vitro and in vivo experiments indicated that for CPO, protection of target brain AChE is afforded by both CaE and AEST, whereas for PO, protection is primarily from CaE.