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Selenium abates manganese–induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats

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Abstract

Excessive exposure to manganese (Mn) is associated with neurotoxicity characterized by oxidative stress, inflammation, and apoptosis induction. Selenium (Se) has been shown to possess antioxidant, anti-inflammatory, and anti-apoptotic properties in humans and animals. The present study investigated the neuroprotective mechanism of Se in rats sub-chronically treated with Mn at 30 mg/kg body weight or orally co-treated with Se at 0.2 and 0.4 mg/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were recorded and computed with the aid of ANY-Maze (a video-tracking software) for 5-min trial, in a novel apparatus. The ANY-Maze analysis showed that Se significantly (p < 0.05) abated Mn-induced locomotive impairment evidenced by increased in maximum speed, total time traveled, absolute turn angle, number of line crossing, rotation and forelimb grip and decreased total time immobile, grooming, and negative geotaxis as verified by the enhanced track plot density. Furthermore, the striatum and hippocampus of the rats were excised and the levels of Mn and Se, oxidative stress markers, proinflammatory cytokines including acetylcholinesterase and caspase-3 activities were assayed. The result shows that Se abates Mn-mediated accumulation of Mn. Also, Se ameliorated Mn-induced decrease in antioxidant enzymes as well as glutathione level and increase in acetylcholinesterase activity, lipid peroxidation, proinflammatory cytokines (i.e., interleukin (IL)-6, IL-1β, tumor necrosis factor alpha), and caspase-3 activation in the striatum and hippocampus of the rats. Collectively, Se abated Mn-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats. Se may serve as a neuroprotective agent against Mn-mediated neurotoxicity.

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Authors and Affiliations

  1. Public Health, Operation Unit, Hydrocarbon Pollution Remediation Project, Aba – Port Harcourt Expressway, Port Harcourt, 350, Rivers State, Nigeria

    Kpobari W. Nkpaa

  2. Department of Pharmacy, University of Port Harcourt Teaching Hospital, Choba, Port Harcourt, Rivers State, Nigeria

    Bright B. Nkpaa

  3. Department of Biochemistry, Faculty of Science, University of Port Harcourt, Choba, Port Harcourt, P.M.B 5323, Rivers State, Nigeria

    Benjamin A. Amadi, Donatus C. Belonwu, Kingsley C. Patrick-Iwuanyanwu, Eucharia O. Nwaichi & Matthew O. Wegwu

  4. School of Life Sciences, Keele University, Staffordshire, ST5 5BG, UK

    Atieme J. Ogbolosingha

  5. Department of Biochemistry, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, Port Harcourt, Rivers State, Nigeria

    Iheanyichukwu Wopara

  6. World Bank Africa Centre of Excellence in Public Health and Toxicological Research (PUTOR), University of Port Harcourt, Port Harcourt, PMB,5323 , Rivers State, Nigeria

    Kingsley C. Patrick-Iwuanyanwu, Eucharia O. Nwaichi & Orish E. Orisakwe

  7. Department of Experimental Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Port Harcourt, Choba, Port Harcourt, P.M.B 5323, Rivers State, Nigeria

    Orish E. Orisakwe

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  1. Kpobari W. Nkpaa
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Correspondence to Kpobari W. Nkpaa.

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Nkpaa, K.W., Nkpaa, B.B., Amadi, B.A. et al. Selenium abates manganese–induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats. Psychopharmacology 239, 399–412 (2022). https://doi.org/10.1007/s00213-021-06010-7

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