Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects

Are they mediated by analogous mechanisms of action?

Caridad López-Granero, Fernando Cañadas, Diana Cardona, Yingchun Yu, Estela Giménez, Rafael Lozano, Daiana Silva Avila, Michael Aschner, Fernando Sánchez-Santed

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)206-216
Number of pages11
JournalToxicological Sciences
Volume131
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Parathion
Isoflurophate
Chlorpyrifos
Oxidative stress
Organophosphates
Oxidative Stress
Acetylcholinesterase
Brain
F2-Isoprostanes
Rats
Experiments
Alternative Splicing
Dinoprostone
Gene expression
Prostaglandins
Toxicity
Wistar Rats
Hippocampus
Genes
Gene Expression

Keywords

  • Acetylcholinesterase
  • Acylpeptide hydrolase
  • Organophosphates
  • Oxidative stress
  • Read-through AchE
  • Spatial learning

ASJC Scopus subject areas

  • Toxicology

Cite this

Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects : Are they mediated by analogous mechanisms of action? / López-Granero, Caridad; Cañadas, Fernando; Cardona, Diana; Yu, Yingchun; Giménez, Estela; Lozano, Rafael; Avila, Daiana Silva; Aschner, Michael; Sánchez-Santed, Fernando.

In: Toxicological Sciences, Vol. 131, No. 1, 01.2013, p. 206-216.

Research output: Contribution to journalArticle

López-Granero, Caridad ; Cañadas, Fernando ; Cardona, Diana ; Yu, Yingchun ; Giménez, Estela ; Lozano, Rafael ; Avila, Daiana Silva ; Aschner, Michael ; Sánchez-Santed, Fernando. / Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects : Are they mediated by analogous mechanisms of action?. In: Toxicological Sciences. 2013 ; Vol. 131, No. 1. pp. 206-216.
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