title: High concentration of trichlorfon (1mM) disrupts axonal cytoskeleton and decreases the expression of plasticity-related proteins in SH-SY5Y cells.
abstract: Some organophosphorus compounds (OPs) induce a neurodegenerative disorder known as organophosphate-induced delayed neuropathy (OPIDN), which is related to irreversible inhibition of neuropathy target esterase (NTE) and impairment of neurite outgrowth. The present study addresses the effects of trichlorfon, mipafox (neuropathic model) and paraoxon (non-neuropathic model) on neurite outgrowth and neuroplasticity-related proteins in retinoic-acid-stimulated SH-SY5Y cells, a cellular model widely used to study the neurotoxicity of OPs. Mipafox (20μM) decreased cellular differentiation and the expression of neurofilament 200 (NF-200), growth associated- (GAP-43) and synaptic proteins (synapsin I and synaptophysin); whereas paraoxon (300μM) induced no effect on cellular differentiation, but significant decrease of NF-200, GAP-43, synapsin I and synaptophysin as compared to controls. However, the effects of paraoxon on these proteins were significantly lower than the effects of mipafox. In conclusion, axonal cytoskeletal proteins, as well as axonal plasticity-related proteins are more effectively affected by neuropathic (mipafox) than by non-neuropathic (paraoxon) OPs, suggesting that they might play a role in the mechanism of OPIDN. At high concentration (1mM), trichlorfon induced effects similar to those of the neuropathic OP, mipafox (20μM), but also caused high inhibition of AChE. Therefore, these effects are unlikely to occur in humans at non-lethal doses of trichlorfon.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, FCFRP, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Laís Silva
authors.initials: LS
authors.lastname: Fernandes
authors.affiliation: Instituto de Ciências da Saúde, Universidade Federal de Mato Grosso, ICS/UFMT/CUS, Sinop, MT, Brazil.
authors.forename: Guilherme Luz
authors.initials: GL
authors.lastname: Emerick
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, FCFRP, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Rafaela Scalco
authors.initials: RS
authors.lastname: Ferreira
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, FCFRP, USP, Ribeirão Preto, SP, Brazil.
authors.forename: Neife Aparecida G Dos
authors.initials: NAGD
authors.lastname: Santos
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, FCFRP, USP, Ribeirão Preto, SP, Brazil. Electronic address: acsantos@fcfrp.usp.br.
authors.forename: Antonio Cardozo Dos
authors.initials: ACD
authors.lastname: Santos
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D001369:Axons / Q000187:drug effects*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007531:Isoflurophate / Q000031:analogs & derivatives* / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009473:Neuronal Plasticity; D010261:Paraoxon / Q000633:toxicity*; D016704:Synapsins / Q000378:metabolism; D014236:Trichlorfon / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D019922:GAP-43 Protein; D007306:Insecticides; D016704:Synapsins; D007531:Isoflurophate; C005238:mipafox; D014236:Trichlorfon; D007770:L-Lactate Dehydrogenase; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; D010261:Paraoxon
keywords: Axonal growth; Neurofilament; Organophosphate-induced delayed neuropathy (OPIDN); Synaptogenesis; Trichlorfon