title: Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration.
abstract: Organophosphates (OPs) are important toxic compounds commonly used for a variety of purposes in agriculture, industry and household settings. It has been well established that the main mechanism of acute toxic action of OP is the inhibition of acetylcholinesterase (AChE). However, we observed long term deficit after acute subcutaneous exposure to Chlorpyrifos (CPF) even when AChE activity is restored. In fact, besides AChE inhibition, non-AChE targets have also been proposed as an alternative mechanism involved in the acute lethal action and side effects of short or long-term exposure. In this context, our main aim in this research was to establish a dose-response curve of Acylpeptide hydrolase (APH) and AChE regional brain activity after acute CPF administration that could explain these long term effects observed in the literature. Moreover, since available data suggest that long term effects of OPs exposure could involve neuronal cell death, our second aim was to evaluate, assessing by Fluoro-Jade B (FJB) staining, whether CPF produces induced cell death. Our results show that an acute exposure to 250 mg/kg CPF does not induce neuronal death as measured by FJB but produces highest AChE regional brain inhibition after administration. In addition, APH seems to be more sensitive than AChE to CPF exposure because after 31 days of exposure, complete recovery was seen only for APH activity at Frontal Cortex, Cerebellum and Brain Stem.
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Cardona
authors.forename: Caridad
authors.initials: C
authors.lastname: López-Granero
authors.forename: Fernando
authors.initials: F
authors.lastname: Cañadas
authors.forename: Jordi
authors.initials: J
authors.lastname: Llorens
authors.forename: Pilar
authors.initials: P
authors.lastname: Flores
authors.forename: Floria
authors.initials: F
authors.lastname: Pancetti
authors.forename: Fernando
authors.initials: F
authors.lastname: Sánchez-Santed
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D016923:Cell Death / Q000187:drug effects*; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D023382:Toxicity Tests, Acute
chemical_list: D002800:Cholinesterase Inhibitors; D005452:Fluoresceins; C435731:fluoro jade; D000110:Acetylcholinesterase; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase; D004390:Chlorpyrifos