In vitro cysteine reactivates organophosphate insecticide dichlorvos-inhibited human cholinesterases

Abstract EN

Objectives : Organophosphate (OP) pesticides inhibit both red blood cell (RBC) and plasma cholinesterases (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.