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

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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.

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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.

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Authors and Affiliations

  1. Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Lalit P. Chandravanshi

  2. Developmental Toxicology Division, CSIR—Indian Institute of Toxicology Research, Post Box No. 80, MG Marg, Lucknow, 226 001, India

    Lalit P. Chandravanshi & Richa Gupta

  3. Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, India

    Rajendra K. Shukla

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Correspondence to Lalit P. Chandravanshi.

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Chandravanshi, L.P., Gupta, R. & Shukla, R.K. Developmental Neurotoxicity of Arsenic: Involvement of Oxidative Stress and Mitochondrial Functions. Biol Trace Elem Res 186, 185–198 (2018). https://doi.org/10.1007/s12011-018-1286-1

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