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
Related Articles
- EP ID EP14792
- DOI 10.18295/squmj.2017.17.03.006
- Views 411
- Downloads 18
Fundamentals of Psychology
From Transplant to Tablets A paradigm shift in Oncology
The Role of Pharmacokinetics and Pharmacodynamics in Early Drug Development with reference to the Cyclin-dependent Kinase (Cdk) Inhibitor - Roscovitine
Pharmacokinetics, pharmacodynamics and pharmacogenetics play an important role in drug discovery and contribute to treatment success. Tis is an essential issue in cancer treatment due to its high toxicity. During the l...
Care of Patients with Diabetic Foot Disease in Oman
Diabetes mellitus is a major public health challenge and causes substantial morbidity and mortality worldwide. Diabetic foot disease is one of the most debilitating and costly complications of diabetes. While simple pr...
Second National Update on Chronic Obstructive Pulmonary Disease (COPD) Oman Respiratory Society and Sultan Qaboos University 14th October 2010