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Neurotoxicity Research

, Volume 35, Issue 1, pp 150–159 | Cite as

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

  • Laís Silva Fernandes
  • Neife Aparecida G. dos Santos
  • Guilherme Luz Emerick
  • Antonio Cardozo dos Santos
ORIGINAL ARTICLE
  • 85 Downloads

Abstract

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 1β 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.

Keywords

Liraglutide Mipafox Organophosphate-induced delayed neuropathy (OPIDN) Neuroplasticity Neuroprotection 

Notes

Funding Information

This study received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grants 307657/2016-7 and 140105/2015-8) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grants 2012/00168-6, 2012/16319-3 and 2013/26906-6).

Compliance with Ethical Standards

Conflict of Interest Statement

The authors declare that they have no conflicts of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Laís Silva Fernandes
    • 1
  • Neife Aparecida G. dos Santos
    • 1
  • Guilherme Luz Emerick
    • 2
  • Antonio Cardozo dos Santos
    • 1
  1. 1.Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto—FCFRPUniversidade de São Paulo, USPRibeirão PretoBrazil
  2. 2.Instituto de Ciências da SaúdeUniversidade Federal de Mato Grosso—ICS/UFMT/CUSSinopBrazil

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