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Biochemical and Molecular Alterations Following Arsenic-Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Brain

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Abstract

Oxidative stress is associated with the generation of reactive oxygen species (ROS), which is supposed to be one of the mechanisms of arsenic-induced neurodegeneration. Mitochondria, being the major source of ROS generation may present an important target of arsenic-mediated neurotoxicity. Hence, we planned the study to elucidate the possible biochemical and molecular alterations induced by arsenic exposure in rat brain mitochondria. Chronic sodium arsenite treatment (25 ppm for 12 weeks) resulted in decreased activity of mitochondrial complexes I, II, and IV followed by increased ROS generation. There was decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rat brain further showing increased superoxide radical generation in mitochondria. The decrease in MnSOD activity might be responsible for the increased protein and lipid oxidation as observed in our study. Protein and messenger RNA (mRNA) levels of MnSOD and mitochondrial uncoupling protein 2 (UCP-2) were downregulated suggesting decreased removal of ROS in rat brain. Fourier transform infrared (FTIR) spectroscopy analysis revealed significant decrease in amide A, amide I, amide II, and Olefinic = CH stretching band area suggesting molecular alteration in proteins and lipids after arsenic treatment. The results of present study indicate that arsenic-induced disturbed mitochondrial metabolism, decreased removal of ROS, decrease in protein synthesis, and altered membrane lipid polarity and fluidity may be responsible for the mitochondrial oxidative damage in rat brain that may further be implicated as contributing factor in arsenic-induced neurodegeneration.

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Acknowledgments

The financial assistance for the present work was provided by Science and Engineering Research Board (SERB), Department of Science and Technology (DST), New Delhi (grant No SR/FT/LS-25/2012), India in the form of Fast Track Young Scientist project sanctioned to Vijay Kumar.

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  1. Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India

    Chandra Prakash, Manisha Soni & Vijay Kumar

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  1. Chandra Prakash
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  2. Manisha Soni
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  3. Vijay Kumar
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Correspondence to Vijay Kumar.

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Prakash, C., Soni, M. & Kumar, V. Biochemical and Molecular Alterations Following Arsenic-Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Brain. Biol Trace Elem Res 167, 121–129 (2015). https://doi.org/10.1007/s12011-015-0284-9

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