The effect of PON1 enhancers on reducing acetylcholinesterase inhibition following organophosphate anticholinesterase exposure in rats.

摘要: Novel nucleophiles, a series of substituted phenoxyalkyl pyridinium oximes, have been previously shown by our laboratories to enhance in vitro paraoxonase 1 (PON1)-mediated degradation sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) and VX ethyl NEMP). Five the most efficacious these nucleophiles were tested rats for their ability reduce level acetylcholinesterase (AChE) inhibition brain peripheral tissues following exposure NIMP or NEMP. Following simultaneous administration nucleophile plus (at 3 dosages yielding about 10-50% AChE at 15 min), all five reduced dosages, lowest dosage. Protective effects seen only short period time, i.e., min. Even though are they not effective reactivators so it is unlikely that resultant decreases from appreciable reactivation. It likely protective are, least part, result enhancement PON1-mediated degradation, an unprecedented mechanism therapy has potential be developed into nerve agent countermeasure.