In Vitro Cysteine Reactivates Organophosphate Insecticide Dichlorvos-Inhibited Human Cholinesterases

Sultan Qaboos Univ Med J. 2017 Aug;17(3):e293-e300. doi: 10.18295/squmj.2017.17.03.006. Epub 2017 Oct 10.

Abstract

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.

Keywords: Antidotes; Cholinesterases; Cysteine; N-Acetylcysteine; Organophosphate Poisoning; Pralidoxime Compounds.

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Antidotes
  • Cholinesterase Inhibitors*
  • Cholinesterase Reactivators / therapeutic use*
  • Cholinesterases / blood*
  • Cholinesterases / drug effects
  • Cysteine / pharmacology*
  • Dichlorvos
  • Enzyme Activation*
  • Erythrocytes / enzymology
  • Feasibility Studies
  • Humans
  • In Vitro Techniques
  • Insecticides
  • Iran
  • Organophosphate Poisoning / drug therapy*
  • Organophosphate Poisoning / enzymology
  • Pralidoxime Compounds / therapeutic use

Substances

  • Antidotes
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Insecticides
  • Pralidoxime Compounds
  • Dichlorvos
  • Cholinesterases
  • Cysteine
  • Acetylcysteine