Organophosphate-induced delayed neuropathy: in vitro studies of mechanisms of neurotoxicity and neuroprotection

• Grant number: 12/00168-6
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2012
• Effective date (End): February 28, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal researcher: Antonio Cardozo dos Santos
• Grantee: Guilherme Luz Emerick
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The indiscriminate use of pesticides as a strategy to increase the agricultural productivity has increased the intoxication incidence. Due to the large number of voluntary or involuntary cases of organophosphates (OPs) intoxication, it is necessary to elucidate the mechanism of the irreversible cellular degeneration characteristic of organophosphate-induced delayed neuropathy (OPIDN). The OPs that cause this type of neuropathy are widely used in chemical industry and agriculture, not only in Brazil but worldwide. It is known that after the neuropathic OP intoxication it occurs approximately 70-80% of inhibition and aging of an esterase known as neuropathy target esterase (NTE), which leads to a series of events that cause axonal degeneration Wallerian-type. In previous studies, our group of work have found a decrease in extracellular calcium and an increase in the activity of some calcium-dependent intracellular proteases, which suggests that after NTE inhibition, calcium migrates to the intracellular environment. However, the mechanism and the sequence of events involved in the development of OPIDN remain unclear. Thus, this study aims to assess in a cell culture model (SH-SY5Y), the mechanism of toxicity of some of the neuropathic OPs most used in Brazil, with focus on the events associated with excessive influx of calcium in the cell. Additionally, the study will also address the effects of compounds which are potentially able to interfere in some point of this sequence of events as a possible protection strategy against OPIDN. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES, LAIS SILVA; DOS SANTOS, NEIFE APARECIDA G.; EMERICK, GUILHERME LUZ; DOS SANTOS, ANTONIO CARDOZO. The Antidiabetic Drug Liraglutide Minimizes the Non-Cholinergic Neurotoxicity of the Pesticide Mipafox in SH-SY5Y Cells. NEUROTOXICITY RESEARCH, v. 35, n. 1, p. 150-159, JAN 2019. Web of Science Citations: 4.

EMERICK, GUILHERME L.; FERNANDES, LAIS S.; DE PAULA, ELOISA SILVA; BARBOSA, JR., FERNANDO; GUINAIM DOS SANTOS, NEIFE APARECIDA; DOS SANTOS, ANTONIO CARDOZO. In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon. TOXICOLOGY IN VITRO, v. 29, n. 5, p. 1079-1087, AUG 2015. Web of Science Citations: 7.

EMERICK, GUILHERME L.; DEOLIVEIRA, GEORGINO H.; DOS SANTOS, ANTONIO C.; EHRICH, MARION. Mechanisms for consideration for intervention in the development of organophosphorus-induced delayed neuropathy. Chemico-Biological Interactions, v. 199, n. 3, p. 177-184, SEP 30 2012. Web of Science Citations: 21.