In Vitro Cysteine Reactivates Organophosphate Insecticide Dichlorvos-Inhibited Human Cholinesterases
Journal Title: Sultan Qaboos University Medical Journal - Year 2017, Vol 17, Issue 3
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. Te 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: Tis 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 (fnal 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: Tese 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.
Authors and Affiliations
Hamidreza Mohammadi| Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute and Department of Toxicology & Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran, Jafar Jalilian| Department of Toxicology & Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran, Mohammad Y. Karimi| Razi Drug Research Center, School of Pharmacy, International Campus, Iran University of Medical Sciences, Tehran, Iran, Seyed V. Shetab-Boushehri| Razi Drug Research Center and Department of Toxicology & Pharmacology, School of Pharmacy, International Campus, Iran University of Medical Sciences, Tehran, Iran
Keywords
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- EP ID EP14792
- DOI 10.18295/squmj.2017.17.03.006
- Views 397
- Downloads 18
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