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Effects of Paraoxon Exposure on Expression of Apoptosis-Related Genes, Neuronal Survival, and Astrocyte Activation in Rat Prefrontal Cortex

  • Zohreh Zare
  • Mohsen Tehrani
  • Sam Zarbakhsh
  • Hamed Farzadmanesh
  • Sakineh Shafia
  • Mahmood Abedinzade
  • Anahita Ghanaat
  • Moslem MohammadiEmail author
Original Article

Abstract

Paraoxon is the bioactive metabolite of organophosphate (OP) pesticide, parathion. This study aimed to evaluate the expression of apoptosis-related genes and histopathological changes in rat prefrontal cortex following exposure to three different doses of paraoxon. Paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male Wistar rats. After 14 or 28 days, mRNA and protein levels of Bax, Bcl-2, and caspase-3 were measured in prefrontal cortex using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. In addition, neuronal injury and astrocyte activation were assessed using cresyl violet staining and glial fibrillary acidic protein (GFAP) immune–positive cells, respectively. Treatment with 0.7 and 1 mg/kg of paraoxon increased mRNA and protein levels of Bax and caspase-3 at 14 and 28 days post-exposure, while mRNA and protein levels of Bcl-2 decreased only in 1 mg/kg group after 14 days. Furthermore, a significant decrease in the number of neurons and a significant increase in the number of GFAP-positive cells were observed in rats receiving 0.7 and 1 mg/kg of paraoxon at both time points. Collectively, our results showed that apoptosis is a major mechanism for neuronal damage after exposure to paraoxon. Also, paraoxon-induced neuronal loss was correlated with activation of astrocytes. Since paraoxon-induced neuronal damage is closely related to convulsion, clinical management of convulsion could protect neuronal brain damage.

Keywords

Paraoxon Prefrontal cortex Astrocyte Apoptosis Glial fibrillary acidic protein Caspase-3 

Notes

Funding Information

This work was financially supported by the Molecular and Cell Biology Research Center of Mazandaran University of Medical Sciences (7181).

Compliance with Ethical Standards

All animal experiments were approved by the Ethical Committee of the Mazandaran University of Medical Sciences, Sari, Iran (IR.MAZUMS.REC.96.7181).

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zohreh Zare
    • 1
  • Mohsen Tehrani
    • 2
  • Sam Zarbakhsh
    • 3
  • Hamed Farzadmanesh
    • 3
  • Sakineh Shafia
    • 4
  • Mahmood Abedinzade
    • 5
  • Anahita Ghanaat
    • 4
  • Moslem Mohammadi
    • 4
    Email author
  1. 1.Department of Anatomical Sciences, Molecular and Cell Biology Research Center, School of MedicineMazandaran University of Medical SciencesSariIran
  2. 2.Department of Immunology, Gastrointestinal Cancer Research Center, School of MedicineMazandaran University of Medical SciencesSariIran
  3. 3.Nervous System Stem Cells Research CenterSemnan University of Medical SciencesSemnanIran
  4. 4.Department of Physiology, Molecular and Cell Biology Research Center, School of MedicineMazandaran University of Medical SciencesSariIran
  5. 5.Medical Biotechnology Research Center, School of ParamedicineGuilan University of Medical SciencesRashtIran

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