Comparative in vitro study of the inhibition of human and hen esterases by methamidophos enantiomers

Autor(es)

Emerick, Guilherme L. ^[1] ; DeOliveira, Georgino H. ^[1] ; Oliveira, Regina V. ^[2] ; Ehrich, Marion ^[3]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Fed Sao Carlos UFSCar, Dept Chem, Sao Carlos, SP - Brazil

^[3] Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 - USA

• Tipo de documento: Artigo Científico
• Fonte: Toxicology; v. 292, n. 2-3, p. 145-150, FEB 26 2012.
• Citações Web of Science: 16

Resumo

The current Organisation for Economic Co-operation and Development (OECD) guidelines for evaluating organophosphorus-induced delayed neuropathy (OPIDN) require the observation of dosed animals over several days and the sacrifice of 48 hens. Adhering to these protocols in tests with enantiomers is difficult because large quantities of the compound are needed and many animals must be utilized. Thus, developing an in vitro screening protocol to evaluate chiral organophosphorus pesticides (OPs) that can induce delayed neuropathy is important. This work aimed to evaluate, in blood and brain samples from hens, human blood, and human cell culture samples, the potential of the enantiomeric forms of methamidophos to induce acetylcholinesterase (AChE) inhibition and/or delayed neurotoxicity. Calpain activation was also evaluated in the hen brain and SH-SY5Y human neuroblastoma cells. The ratio between the inhibition of neuropathy target esterase (NTE) and AChE activities by the methamidophos enantiomers was evaluated as a possible indicator of the enantiomers' abilities to induce OPIDN. The (-)-methamidophos exhibited an IC50 value approximately 6 times greater than that of the (+)-methamidophos for the lymphocyte NTE (LNTE) of hens, and (+)-methamidophos exhibited an IC50 value approximately 7 times larger than that of the (-)-methamidophos for the hen brain AChE. The IC50 values were 7 times higher for the human erythrocyte AChE and 5 times higher for AChE in the SH-SY5Y human neuroblastoma cells. Considering the esterases inhibition and calpain results, (+)-methamidophos would be expected to have a greater ability to induce OPIDN than the (-)-methamidophos in humans and in hens. (C) 2011 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 09/51048-8 - Avaliação de neurotoxicidade de formas enantioméricas de praguicidas organofosforados: um estudo comparativo em células humanas e de galinhas
• Beneficiário: Guilherme Luz Emerick
• Modalidade de apoio: Bolsas no Brasil - Doutorado