title: Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects: are they mediated by analogous mechanisms of action?
abstract: Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative damage. Little is known about the relationship between behavioral deficits and oxidative stress within the context of such exposures. Accordingly, the first experiment was carried out to address this issue. Male Wistar rats were administered 250 mg/kg of chlorpyrifos (CPF), 1.5 mg/kg of diisopropylphosphorofluoridate (DFP), or 15 mg/kg of parathion (PTN). Spatial learning in the water maze task was evaluated, and F(2)-isoprostanes (F(2)-IsoPs) and prostaglandin (PGE(2)) were analyzed in the hippocampus. A second experiment was designed to determine the degree of inhibition of brain acetylcholinesterase (AChE) activity, both the soluble and particulate forms of the enzyme, and to assess changes in AChE gene expression given evidence on alternative splicing of the gene in response to OP exposures. In addition, brain acylpeptide hydrolase (APH) activity was evaluated as a second target for OP-mediated effects. In both experiments, rats were sacrificed at various points to determine the time course of OPs toxicity in relation to their mechanism of action. Results from the first experiment suggest cognitive and emotional deficits after OPs exposure, which could be due to, at least in part, increased F(2)-IsoPs levels. Results from the second experiment revealed inhibition of brain AChE and APH activity at various time points post OP exposure. In addition, we observed increased brain read-through splice variant AChE (AChE-R) mRNA levels after 48 h PTN exposure. In conclusion, this study provides novel data on the relationship between cognitive alterations and oxidative stress, and the diverse mechanisms of action along a temporal axis in response to OP exposures in the rat.
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, La Cañada, 04120 Almería, Spain.
authors.forename: Caridad
authors.initials: C
authors.lastname: López-Granero
authors.forename: Fernando
authors.initials: F
authors.lastname: Cañadas
authors.forename: Diana
authors.initials: D
authors.lastname: Cardona
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Yu
authors.forename: Estela
authors.initials: E
authors.lastname: Giménez
authors.forename: Rafael
authors.initials: R
authors.lastname: Lozano
authors.forename: Daiana Silva
authors.initials: DS
authors.lastname: Avila
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: Fernando
authors.initials: F
authors.lastname: Sánchez-Santed
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004390:Chlorpyrifos / Q000633:toxicity*; D015232:Dinoprostone / Q000378:metabolism; D028441:F2-Isoprostanes / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007531:Isoflurophate / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010278:Parathion / Q000633:toxicity*; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D028441:F2-Isoprostanes; D007531:Isoflurophate; D010278:Parathion; D000110:Acetylcholinesterase; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase; D004390:Chlorpyrifos; D015232:Dinoprostone