In vitro study of the neuropathic potential of the organophosphorus compounds trichlorfon and acephate

Autor(es)

Fernandes, Lais S. ^[1] ; Emerick, Guilherme L. ^{[1, 2]} ; dos Santos, Neife Aparecida G. ^[1] ; de Paula, Eloisa Silva ^[1] ; Barbosa, Jr., Fernando ^[1] ; dos Santos, Antonio Cardozo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo USP RP, Fac Ciencias Farmaceut Ribeirao Preto, DACTB, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Mato Grosso, UFMT CUS, ICS, Dept Farm, Sinop, MT - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGY IN VITRO; v. 29, n. 3, p. 522-528, APR 2015.
• Citações Web of Science: 15

Resumo

Organophosphorus-induced delayed neuropathy (OPIDN) is a central and peripheral distal axonopathy characterized by ataxia and paralysis. Trichlorfon and acephate are two organophosphorus compounds (OPs) used worldwide as insecticide and which cause serious effects to non-target species. Despite that, the neuropathic potential of these OPs remains unclear. The present study addressed the neurotoxic effects and the neuropathic potential of trichlorfon and acephate in SH-SY5Y human neuroblastoma cells, by evaluating inhibition and aging of neuropathy target esterase (NTE), inhibition of acetylcholinesterase (AChE), neurite outgrowth, cytotoxicity and intracellular calcium. Additionally, the effects observed were compared to those of two well-studied OPs: mipafox (known as neuropathic) and paraoxon (known as non-neuropathic). Trichlorfon and mipafox presented the lowest percentage of reactivation of inhibited NTE and the lowest ratio IC50 NTE/IC50 AChE. Moreover, they caused inhibition and aging of at least 70% of the activity of NTE at sub-lethal concentrations. All these effects have been associated with induction of OPIDN. When assayed at these concentrations, trichlorfon and mipafox reduced neurite outgrowth and increased intracellular calcium, events implicated in the development of OPIDN. Acephate caused effects similar to those caused by paraoxon (non-neuropathic OP) and was only able to inhibit 70% of NTE activity at lethal concentrations. These findings suggest that trichlorfon is potentially neuropathic, whereas acephate is not. (c) 2015 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/16319-3 - Estudo in vitro dos mecanismos de neurotoxicidade do organofosforado triclorfom: estratégias de neuroproteção
• Beneficiário: Lais da Silva Fernandes
• Linha de fomento: Bolsas no Brasil - Mestrado