Organophosphate-based pesticides inhibit acetylcholinesterase (AChE), which plays a pivotal role in neuromuscular function. While spraying in the field, farmworkers get exposed to pesticides through the dermal route. Internalized pesticide inhibits AChE, which leads to neurotoxicity, cardiotoxicity, cognitive dysfunction, loss of endurance, and death in severe cases. Here, we present a nucleophilic pyridine-2-aldoxime-functionalized chitosan-based topical gel (poly-Oxime gel) that rapidly deactivates organophosphates, methyl parathion (MPT), on the skin of rats, which leads to reduced AChE inhibition in the blood and tissues. Testing the robustness of poly-Oxime gel, we report reduction in AChE inhibition following repeated dermal administration of MPT in the presence of poly-Oxime gel. Furthermore, poly-Oxime gel prevented MPT-induced neuromuscular dysfunction, loss of endurance, and locomotor coordination. We observe a 100% survival in rats following topical MPT administration in the presence of poly-Oxime gel. This prophylactic gel may therefore help farmworkers by limiting pesticide-induced toxicity and mortality.

中文翻译：

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亲核聚肟局部用凝胶预防农药引起的神经元功能障碍和死亡。

基于有机磷酸酯的农药抑制乙酰胆碱酯酶（AChE），后者在神经肌肉功能中起关键作用。在田间喷洒时，农场工人会通过皮肤途径接触农药。内化农药会抑制AChE，在严重情况下会导致神经毒性，心脏毒性，认知功能障碍，耐力丧失和死亡。在这里，我们介绍了一种亲核吡啶-2-醛肟功能化的壳聚糖基局部用凝胶（聚-肟凝胶），该凝胶可在大鼠皮肤上快速失活有机磷酸酯，甲基对硫磷（MPT），从而降低血液中对AChE的抑制作用和组织。为了测试聚肟凝胶的健壮性，我们报告了在有下列药物存在的情况下反复经皮给予MPT后，AChE抑制作用降低。聚肟凝胶。此外，聚肟凝胶可预防MPT诱导的神经肌肉功能障碍，耐力丧失和运动协调。我们观察到，在存在聚-肟凝胶的情况下，局部MPT给药后，大鼠的存活率为100％。因此，这种预防性凝胶可通过限制农药引起的毒性和死亡率来帮助农民工。