In vitro cysteine reactivates organophosphate insecticide dichlorvos-inhibited human cholinesterases

Objectives: organophosphate (op) pesticides inhibit both red blood cell (rbc) and plasma cholin-esterases (ches). oximes,especially pralidoxime (2-pam),are widely used as antidotes to treat op poisoning. in addition,n-acetylcysteine (nac) is sometimes used as an adjuvant antidote. the current study aimed to assess the feasibility of using nac as a single therapeutic agent for op poisoning in comparison to in vitro 2-pam. methods: this study was carried out at the razi drug research center of iran university of medical sciences,tehran,iran,between april and september 2014. a total of 22 healthy human subjects were recruited and 8 ml citrated blood samples were drawn from each subject. dichlorvos-inhibited blood samples were separately exposed to low and high doses (final concentrations of 300 and 600 μmol.l-1,respectively) of 2-pam,nac and cysteine. plasma and rbcs were then separated by centrifugation and their che activity was measured using spectrophotometry. results: although cysteine—and not nac—increased the che activity of both plasma and rbcs over those of dichlorvos,it did not increase them over those of a high dose of 2-pam. conclusion: these results suggest that the direct reactions of 2-pam and cysteine with dichlorvos and the reactivation of phosphorylated ches occurr via an associative stepwise addition-elimination process. high therapeutic blood concentrations of cysteine are needed for the elevation of che activity in plasma and rbcs; however,both this agent and nac may still be effective in the reactivation of plasma and rbc ches. © 2017,sultan qaboos university. all rights reserved.