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Prevention of pesticide-induced neuronal dysfunction and mortality with nucleophilic poly-Oxime topical gel. [BIG Grant Supported Entrepreneur]

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TitlePrevention of pesticide-induced neuronal dysfunction and mortality with nucleophilic poly-Oxime topical gel. [BIG Grant Supported Entrepreneur]
Publication TypeJournal Article
Year of Publication2018
AuthorsThorat K, Pandey S, Chandrashekharappa S, Vavilthota N, Hiwale AA, Shah P, Sreekumar S, Upadhyay S, Phuntsok T, Mahato M, Mudnakudu-Nagaraju KK, Sunnapu O, Vemula PK
JournalSci Adv
Volume4
Issue10
Paginationeaau1780
Date Published2018 Oct
ISSN2375-2548
Abstract

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 (-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 -Oxime gel, we report reduction in AChE inhibition following repeated dermal administration of MPT in the presence of -Oxime gel. Furthermore, -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 -Oxime gel. This prophylactic gel may therefore help farmworkers by limiting pesticide-induced toxicity and mortality.

DOI10.1126/sciadv.aau1780
Alternate JournalSci Adv
PubMed ID30345360
PubMed Central IDPMC6192682