In vitro Reactivating Effects of Standard and Newly Developed Oximes on Malaoxon‐Inhibited Mouse Brain Acetylcholinesterase |
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| Authors: | Alessandra Antunes Dos Santos Danúbia Bonfanti Dos Santos Alcir Luiz Dafre Andreza Fabro De Bem Diogo Onofre Souza João Batista Teixeira Da Rocha Kamil Kuca Marcelo Farina |
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| Affiliation: | 1. Departamento de Bioquímica;2. Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil;3. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;4. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil;5. Centre of Advanced Studies and Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, Czech Republic |
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| Abstract: | Abstract: Malathion is an organophosphate (OP) pesticide whose toxicity depends on its bioactivation to malaoxon. Human malathion poisoning has been treated with oximes (mainly pralidoxime) in an attempt to reactivate OP‐inhibited acetylcholinesterase (AChE). However, pralidoxime has shown unsatisfactory therapeutic effects in malathion poisoning and its routine use has been questioned. In this study, we evaluated the in vitro potency of standards and newly developed oximes in reactivating malaoxon‐inhibited AChE derived from mouse brain supernatants. Malaoxon displayed a concentration‐dependent inhibitory effect on mouse brain AChE (IC50 = 2.36 μM), and pralidoxime caused a modest reactivating effect (30% of reactivation at 600 μM). Obidoxime and trimedoxime, as well as K047 and K075, displayed higher reactivating effects (from 55% to 70% of reactivation at 600 μM) when compared with pralidoxime. The results show that obidoxime, trimedoxime, K074 and K075 present higher reactivating effects on malaoxon‐inhibited AChE under in vitro conditions when compared with pralidoxime. Taking into account the unsatisfactory effects of pralidoxime as antidotal treatment in malathion poisonings, the present results suggest that obidoxime, trimedoxime, K074 and K075 might be interesting therapeutic strategies to reactivate malaoxon‐inhibited AChE in malathion poisonings. |
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