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Food Chemistry Aug 2023Herein, we developed a method coupling TLC and enzyme inhibition principles to rapidly detect OPs (dichlorvos, paraoxon and parathion). After the removal of the organic...
Herein, we developed a method coupling TLC and enzyme inhibition principles to rapidly detect OPs (dichlorvos, paraoxon and parathion). After the removal of the organic solvent from the samples using TLC and paper-based chips, the enzyme was added to the detection system. The results showed that the current method effectively reduced the effects of solvents on enzyme behavior. Moreover, the pigments could be successfully retained on TLC with 40% ddHO/ACN solution (v/v) as a developing solvent. Additionally, the detection limits (LODs) were 0.002 µg/mL for dichlorvos, 0.006 µg/mL for paraoxon, and 0.003 µg/mL for parathion. Finally, the method was applied to spiked cabbage, cucumber, and spinach and showed good average recoveries ranging between 70.22% and 119.79%. These results showed that this paper-based chip had high sensitivity, precleaning, and elimination of organic solvent properties. Furthermore, it provides a valuable idea for sample pretreatment and rapid determination of pesticide residues in food.
Topics: Pesticides; Dichlorvos; Chromatography, Thin Layer; Paraoxon; Pesticide Residues; Parathion; Solvents
PubMed: 36893638
DOI: 10.1016/j.foodchem.2023.135822 -
Journal of Neurochemistry Apr 2024Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human...
A single post-exposure oxime RS194B treatment rapidly reactivates acetylcholinesterase and reverses acute symptoms in macaques exposed to diethylphosphorothioate parathion and chlorpyrifos insecticides.
Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human health. Similar to nerve agents, insecticides are neurotoxins that target and inhibit acetylcholinesterase (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with an oxime to reactivate the OP-inhibited AChE. However, animal model studies and recent clinical trials using insecticide-poisoned individuals have shown minimal clinical benefits of the currently approved oximes and their efficacy as antidotes has been debated. Currently used oximes either reactivate poorly, do not readily cross the blood-brain barrier (BBB), or are rapidly cleared from the circulation and must be repeatedly administered. Zwitterionic oximes of unbranched and simplified structure, for example RS194B, have been developed that efficiently cross the BBB resulting in reactivation of OP-inhibited AChE and dramatic reversal of severe clinical symptoms in mice and macaques exposed to OP insecticides or nerve agents. Thus, a single IM injection of RS194B has been shown to rapidly restore blood AChE and butyrylcholinesterase (BChE) activity, reverse cholinergic symptoms, and prevent death in macaques following lethal inhaled sarin and paraoxon exposure. The present macaque studies extend these findings and assess the ability of post-exposure RS194B treatment to counteract oral poisoning by highly toxic diethylphosphorothioate insecticides such as parathion and chlorpyrifos. These OPs require conversion by P450 in the liver of the inactive thions to the active toxic oxon forms, and once again demonstrated RS194B efficacy to reactivate and alleviate clinical symptoms within 60 mins of a single IM administration. Furthermore, when delivered orally, the Tmax of RS194B at 1-2 h was in the same range as those administered IM but were maintained in the circulation for longer periods greatly facilitating the use of RS194B as a non-invasive treatment, especially in isolated rural settings.
Topics: Animals; Mice; Acetamides; Acetylcholinesterase; Butyrylcholinesterase; Chlorpyrifos; Cholinesterase Inhibitors; Cholinesterase Reactivators; Insecticides; Macaca; Nerve Agents; Organophosphorus Compounds; Oximes; Parathion
PubMed: 36786545
DOI: 10.1111/jnc.15777 -
Drug and Chemical Toxicology Jan 2024A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate...
A series of uncharged salicylaldehyde oximes were synthesized and evaluated for the reactivation of organophosphorus (OP) nerve agents simulants Diethylchlorophosphonate (DCP) & Diethylcyanophosphonate (DCNP) and pesticides (paraoxon & malaoxon) inhibited Acetylcholinesterase AChE). The computational software Swiss ADME and molinspiration were used to unfold the probability of drug-likeness properties of the oximes derivatives. Substituted aromatic oximes with diethylamino or bromo group with free hydroxyl group ortho to oxime moiety were found efficient to regenerate the enzymatic activity in AChE assay. The alkylation of the ortho hydroxyl group of derivatives led to the loss of reactivation potential. The derivatives with a hydroxyl group and without oxime group and vice versa did not show significant reactivation potency against tested OP toxicants. Further, we also evaluated the reactivation potential of these selected molecules on the rat brain homogenate against different OPs inhibited ChE and found maximum reactivation potency of oxime . The results were further validated by molecular docking and dynamic studies which showed that the hydroxyl group interacted with serine amino acids in the catalytic anionic site of AChE enzyme and was stable up to 200 ns consequently providing proper orientation to oxime moiety for reactivating the OP inhibited enzyme. It has thus been proved by the structure-activity relationship of oximes derivatives that hydroxyl group ortho to oxime is essential for reactivating OP inhibited AChE. Amongst the twenty-one oximes derivatives, was found to be most active in regenerating the paraoxon, malaoxon, DCP and DCNP inhibited AChE enzyme.
Topics: Cholinesterase Inhibitors; Paraoxon; Cholinesterase Reactivators; Acetylcholinesterase; Molecular Docking Simulation; Oximes; Organophosphorus Compounds; Malathion; Nitrophenols
PubMed: 36514993
DOI: 10.1080/01480545.2022.2150210