Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5861587 | Toxicology in Vitro | 2015 | 9 Pages |
Abstract
Organophosphorus-induced delayed neuropathy (OPIDN) is a central-peripheral distal axonopathy that develops 8-14Â days after poisoning by a neuropathic organophosphorus compound (OP). Several OPs that caused OPIDN were withdrawn from the agricultural market due to induction of serious delayed effects. Therefore, the development of in vitro screenings able to differentiate neuropathic from non-neuropathic OPs is of crucial importance. Thus, the aim of this study was to evaluate the differences in the neurotoxic effects of mipafox (neuropathic OP) and paraoxon (non-neuropathic OP) in SH-SY5Y human neuroblastoma cells, using the inhibition and aging of neuropathy target esterase (NTE), inhibition of acetylcholinesterase (AChE), activation of calpain, neurite outgrowth, cytotoxicity and intracellular calcium as indicators. Additionally, the potential of fenamiphos and profenofos to cause acute and/or delayed effects was also evaluated. Mipafox had the lowest IC50 and induced the highest percentage of aging of NTE among the OPs evaluated. Only mipafox was able to cause calpain activation after 24Â h of incubation. Concentrations of mipafox and fenamiphos which inhibited at least 70% of NTE were also able to reduce neurite outgrowth. Cytotoxicity was higher in non-neuropathic than in neuropathic OPs while the intracellular calcium levels were higher in neuropathic than in non-neuropathic OPs. In conclusion, the SH-SY5Y cellular model was selective to differentiate neuropathic from non-neuropathic OPs; fenamiphos, but not profenofos presented results compatible with the induction of OPIDN.
Keywords
3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromideToCPSDSTri-ortho-cresyl phosphateAOPTRISNTEIC50OPIDNDTNBINaPATCHOECDNGF5,5′-dithiobis(2-nitrobenzoic acid)MTTAChEEDTAEthylenediaminetetraacetic acidacetylthiocholineAcetylcholinesterasetris(hydroxymethyl) aminomethanestandard error of the meanOrganisation for Economic Co-operation and Developmentsodium dodecyl sulfateOrganophosphorus pesticidesOrganophosphorus pesticideCytotoxicitynerve growth factorNeurite extensionSEMneuropathy target esteraseOrganophosphorus-induced delayed neuropathyCalcium
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Authors
Guilherme L. Emerick, LaÃs S. Fernandes, EloÃsa Silva de Paula, Fernando Jr., Neife Aparecida Guinaim dos Santos, Antonio Cardozo dos Santos,