title: In vitro study of the neuropathic potential of the organophosphorus compounds trichlorfon and acephate.
abstract: 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.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP - USP - Avenida do Café, s/n, Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Laís S
authors.initials: LS
authors.lastname: Fernandes
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP - USP - Avenida do Café, s/n, Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil; Departamento de Farmácia, Instituto de Ciências da Saúde, Universidade Federal de Mato Grosso - ICS/UFMT/CUS, Sinop, MT, Brazil.
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Emerick
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP - USP - Avenida do Café, s/n, Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Neife Aparecida G
authors.initials: NA
authors.lastname: dos Santos
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP - USP - Avenida do Café, s/n, Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Eloísa Silva
authors.initials: ES
authors.lastname: de Paula
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP - USP - Avenida do Café, s/n, Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - FCFRP - USP - Avenida do Café, s/n, Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil. Electronic address: acsantos@fcfrp.usp.br.
authors.forename: Antonio Cardozo
authors.initials: AC
authors.lastname: dos Santos
mesh_terms: D002118:Calcium / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D016501:Neurites / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D063088:Phosphoramides / Q000633:toxicity*; D014236:Trichlorfon / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009946:Organothiophosphorus Compounds; D063088:Phosphoramides; C001969:acephate; D014236:Trichlorfon; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D053148:Caspase 3; D002118:Calcium
keywords: Acephate; Acetylcholinesterase (AChE); Neuropathy target esterase (NTE); Organophosphorus compounds; Organophosphorus-induced delayed neuropathy (OPIDN); Trichlorfon