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Biological Trace Element Research

, Volume 186, Issue 1, pp 185–198 | Cite as

Developmental Neurotoxicity of Arsenic: Involvement of Oxidative Stress and Mitochondrial Functions

  • Lalit P. Chandravanshi
  • Richa Gupta
  • Rajendra K. Shukla
Article

Abstract

Over the last decade, there has been an increased concern about the health risks from exposure to arsenic at low doses, because of their neurotoxic effects on the developing brain. The exact mechanism underlying arsenic-induced neurotoxicity during sensitive periods of brain development remains unclear, although enhanced oxidative stresses, leading to mitochondrial dysfunctions might be involved. Here, we highlight the generation of reactive oxygen species (ROS) and oxidative stress which leads to mitochondrial dysfunctions and apoptosis in arsenic-induced developmental neurotoxicity. Here, the administration of sodium arsenite at doses of 2 or 4 mg/kg body weight in female rats from gestational to lactational (GD6-PD21) resulted to increased ROS, led to oxidative stress, and increased the apoptosis in the frontal cortex, hippocampus, and corpus striatum of developing rats on PD22, compared to controls. Enhanced levels of ROS were associated with decreased mitochondrial membrane potential and the activity of mitochondrial complexes, and hampered antioxidant levels. Further, neuronal apoptosis, as measured by changes in the expression of pro-apoptotic (Bax, Caspase-3), anti-apoptotic (Bcl2), and stress marker proteins (p-p38, pJNK) in arsenic-exposed rats, was discussed. The severities of changes were found to more persist in the corpus striatum than in other brain regions of arsenic-exposed rats even after the withdrawal of exposure on PD45 as compared to controls. Therefore, our results indicate that perinatal arsenic exposure leads to abrupt changes in ROS, oxidative stress, and mitochondrial functions and that apoptotic factor in different brain regions of rats might contribute to this arsenic-induced developmental neurotoxicity.

Keywords

Arsenic Developmental neurotoxicity Oxidative stress Mitochondria Apoptosis 

Notes

Acknowledgements

The authors thank the Director, CSIR—Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, for his support and the keen interest in the present study. Financial support by the University Grants Commission, New Delhi, for carrying out the study is gratefully acknowledged.

Compliance with Ethical Standards

Conflict of Interest

None declared.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lalit P. Chandravanshi
    • 1
    • 2
  • Richa Gupta
    • 2
  • Rajendra K. Shukla
    • 3
  1. 1.Department of Zoology, Institute of ScienceBanaras Hindu UniversityVaranasiIndia
  2. 2.Developmental Toxicology DivisionCSIR—Indian Institute of Toxicology ResearchLucknowIndia
  3. 3.Department of BiochemistryAll India Institute of Medical SciencesBhopalIndia

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