Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotr
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Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment Nandita Medda 1 & Ritesh Patra 1 & Tamal K. Ghosh 2 & Smarajit Maiti 1,3 Received: 3 December 2019 / Accepted: 7 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 Parkinsonismand Alzheimer’s-like symptoms. Our present analysis is helpful for the therapeutic studies on arsenic or other heavy metal associated neurological dysfunction. Keywords Arsenic-induced oxidative stress and neurotoxicity . Blood-brain barrier and antioxidant system . Cognition and mitochondrial membrane . Neurotransmitter and hormonal alteration
Introduction Arsenic is a metalloid element present in the periodic table in 33rd position. It is widely distributed element in the environment. Environmental arsenic can exist in organic or inorganic form. Arsenic in organic states generally considered as nontoxic, whereas inorganic state is toxic. Organic forms are less toxic and poorly absorbed in the cells, whereas inorganic are highly reactive and affect the system through a series of
* Smarajit Maiti [email protected] 1
Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Vidyasagar University, Midnapore, West Bengal 721102, India
2
Department of Health and Family Welfare, Government of West Bengal, Salt Lake, Calcutta, India
3
Epidemiology and Human Health Division, Agricure Biotech Research Society, Midnapore 721101, India
reactions. Excess concentration of arsenic generates oxidative stress by reactive oxygen species (ROS) within subcellular compartments. ROS can directly damage proteins, amino acids, nucleic acid, and membrane lipids [1]. Enzymatic and
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