The Antidiabetic Drug Liraglutide Minimizes the Non-Cholinergic Neurotoxicity of the Pesticide Mipafox in SH-SY5Y Cells

Autor(es)

Fernandes, Lais Silva ^[1] ; dos Santos, Neife Aparecida G. ^[1] ; Emerick, Guilherme Luz ^[2] ; dos Santos, Antonio Cardozo ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Fed Mato Grosso ICS UFMT CUS, Inst Ciencias Saude, Sinop, MT - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROTOXICITY RESEARCH; v. 35, n. 1, p. 150-159, JAN 2019.
• Citações Web of Science: 4

Resumo

Organophosphorus (OPs) compounds have been widely used in agriculture, industry, and household, and the neurotoxicity induced by them is still a cause of concern. The main toxic mechanism of OPs is the inhibition of acetylcholinesterase (AChE); however, the delayed neuropathy induced by OPs (OPIDN) is mediated by other mechanisms such as the irreversible inhibition of 70% of NTE activity (neuropathy target esterase) that leads to axonal degeneration. Liraglutide is a long-lasting GLP-1 analog clinically used as antidiabetic. Its neurotrophic and neuroprotective effects have been demonstrated in vitro and in experimental models of neurodegenerative diseases. As in OPIDN, axonal degeneration also plays a role in neurodegenerative diseases. Therefore, this study investigated the protective potential of liraglutide against the neurotoxicity of OPs by using mipafox as a neuropathic agent (at a concentration able to inhibit and age 70% of NTE activity) and a neuronal model with SH-SY5Y neuroblastoma cells, which express both esterases. Liraglutide protected cells against the neurotoxicity of mipafox by increasing neuritogenesis, the uptake of glucose, the levels of cytoskeleton proteins, and synaptic-plasticity modulators, besides decreasing the pro-inflammatory cytokine interleukin 1 and caspase-3 activity. This is the first study to suggest that liraglutide might induce beneficial effects against the delayed, non-cholinergic neurotoxicity of OPs. (AU)

• Processo FAPESP: 12/16319-3 - Estudo in vitro dos mecanismos de neurotoxicidade do organofosforado triclorfom: estratégias de neuroproteção
• Beneficiário: Lais da Silva Fernandes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/00168-6 - Neuropatia retardada induzida por organofosforados: estudos in vitro dos mecanismos de neurotoxicidade e de neuroproteção
• Beneficiário: Guilherme Luz Emerick
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/26906-6 - Neuropatia retardada induzida por organofosforados: estudo in vitro dos mecanismos de neurotoxicidade do organofosforado triclorfom e estratégias de neuroproteção
• Beneficiário: Antonio Cardozo dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular