In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon

Author(s)

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

Affiliation

^[1] Univ Sao Paulo, FCFRP, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Mato Grosso, Inst Ciencias Saude, Dept Farm, CUS, BR-78557267 Sinop, MT - Brazil

• Document type: Journal article
• Source: TOXICOLOGY IN VITRO; v. 29, n. 5, p. 1079-1087, AUG 2015.
• Web of Science Citations: 7

Abstract

Organophosphorus-induced delayed neuropathy (OPIDN) is a central-peripheral distal axonopathy that develops 8-14 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 Several OPs that caused OPIDN were withdrawn from the agricultural market due to induction of serious delayed effects.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 24 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. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/16319-3 - In vitro study of the mechanisms of neurotoxicity of the organophosphate trichlorfon: strategies for neuroprotection
• Grantee: Lais da Silva Fernandes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/00168-6 - Organophosphate-induced delayed neuropathy: in vitro studies of mechanisms of neurotoxicity and neuroprotection
• Grantee: Guilherme Luz Emerick
• Support Opportunities: Scholarships in Brazil - Post-Doctoral