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Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment

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Abstract

Arsenic toxicity which is now a global concern is predicted to affect more than 200 million people. Chronic arsenic exposure conduce carcinogenicity, hepatotoxicity, and neurotoxicity. Here we have reviewed numerous epidemiological and experimental reports related to arsenic toxicity to explore its neurotoxicity mechanism. Penetrability of this metalloid through blood-brain barrier makes it a potent neuro-toxicant by inducing mitochondrial membrane instability and calorie exhaustion. It directly affects the cortex, cerebellum region, and specially microglial cells by the induction of a variety of pro-inflammatory cytokines like TNF-α, IL-6, etc. Pro-apoptotic signaling and the caspase activation by arsenic initiate large-scale tissue damage. Severe diminution of the antioxidant enzymes like superoxide dismutase, catalase, and GPx increases the tissue damage by reactive oxygen and nitrogen species. Hormonal imbalance and neurotransmitter dysregulations make the neural damage and synergism of so many toxic effects create nonresponsive neural control over multiple organs. That enhances the peripheral major organ damage besides direct arsenic effects on these organs. There is motor and cognitive dysfunction which may initiate Parkinsonism- and Alzheimer’s-like symptoms. Our present analysis is helpful for the therapeutic studies on arsenic or other heavy metal associated neurological dysfunction.

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Correspondence to Smarajit Maiti.

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Medda, N., Patra, R., Ghosh, T.K. et al. Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment. Biol Trace Elem Res (2020). https://doi.org/10.1007/s12011-020-02044-8

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Keywords

  • Arsenic-induced oxidative stress and neurotoxicity
  • Blood-brain barrier and antioxidant system
  • Cognition and mitochondrial membrane
  • Neurotransmitter and hormonal alteration