TY - JOUR
T1 - Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects
T2 - Are they mediated by analogous mechanisms of action?
AU - López-Granero, Caridad
AU - Cañadas, Fernando
AU - Cardona, Diana
AU - Yu, Yingchun
AU - Giménez, Estela
AU - Lozano, Rafael
AU - Avila, Daiana Silva
AU - Aschner, Michael
AU - Sánchez-Santed, Fernando
PY - 2013/1
Y1 - 2013/1
N2 - 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 F2-isoprostanes (F2-IsoPs) and prostaglandin (PGE2) 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 F2-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.
AB - 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 F2-isoprostanes (F2-IsoPs) and prostaglandin (PGE2) 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 F2-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.
KW - Acetylcholinesterase
KW - Acylpeptide hydrolase
KW - Organophosphates
KW - Oxidative stress
KW - Read-through AchE
KW - Spatial learning
UR - http://www.scopus.com/inward/record.url?scp=84872403910&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872403910&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfs280
DO - 10.1093/toxsci/kfs280
M3 - Article
C2 - 22986948
AN - SCOPUS:84872403910
SN - 1096-6080
VL - 131
SP - 206
EP - 216
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -