Selenium and zinc alleviate quaternary metal mixture -induced neurotoxicity in rats by inhibiting oxidative damage and modulating the expressions of NF-kB and Nrf2/Hmox-1 pathway

Chinyere Dike; Chinna N Orish; Anthonet N Ezejiofor; Ana Cirovic; Aleksandar Cirovic; Bolaji Babatunde; Francis Sikoki; Orish E Orisakwe

doi:10.1016/j.ibneur.2023.06.003

Selenium and zinc alleviate quaternary metal mixture -induced neurotoxicity in rats by inhibiting oxidative damage and modulating the expressions of NF-kB and Nrf2/Hmox-1 pathway

IBRO Neurosci Rep. 2023 Jun 16:15:57-67. doi: 10.1016/j.ibneur.2023.06.003. eCollection 2023 Dec.

Authors

Chinyere Dike¹, Chinna N Orish², Anthonet N Ezejiofor¹, Ana Cirovic³, Aleksandar Cirovic³, Bolaji Babatunde⁴, Francis Sikoki⁴, Orish E Orisakwe¹

Affiliations

¹ African Centre of Excellence for Public Health and Toxicological Research (ACE-PUTOR), University of Port Harcourt, PMB, 5323 Port Harcourt, Choba, Nigeria.
² Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Port Harcourt, PMB, 5323 Port Harcourt, Choba, Nigeria.
³ University of Belgrade, Faculty of Medicine, Institute of Anatomy, Belgrade, Serbia.
⁴ Department of Animal and Environmental Biology, Faculty of Science, University of Port Harcourt, PMB, 5323 Port Harcourt, Choba, Nigeria.

Abstract

Background: This study evaluated the potential protective effects of Zn and Se in the cerebellum and cerebral cortex, two fundamentally important brain regions, in albino rats that were exposed to heavy metals mixture (Al, Pb, Hg and Mn).

Methods: Animals were divided into five groups of seven animals per group with following patterns of exposure, controls group 1 were orally treated with deionized water for 60 days; group 2 was exposed to heavy metal mixture (HMM) with following concentrations (20 mg·kg^-1 of Pb body weight; 0.40 mg·kg^-1 of Hg; 0.56 mg·kg^-1 of Mn; and 35 mg·kg^-1; of Al), while groups 3,4 and 5 were exposed to HMM and orally co-treated with zinc chloride (ZnCl₂; 0.80 mg/kg), sodium selenite (Na₂SeO₃;1.50 mg/kg) and zinc chloride plus sodium selenite (ZnCl_0.2 + Na₂SeO₃) respectively.

Results: Exposure to HMM depressed cellular antioxidant apparatus, induced generation of lipid peroxidation markers (Malondialdehyde and NO), downregulated expression of transcription factors (Nrf2, and NF-kB) and upregulated Caspase 3 levels. HMM potentiated acetylcholinesterase activity and induced moderate histopathological alterations. Nevertheless, Zn, Se and in particular Zn + Se had recovering effects on all mentioned hazardous effects produced by HMM exposure in the cerebral cortex and cerebellum.

Conclusions: Selenium and zinc exert neuroprotection via Nrf2/NF-kB signaling pathways against quaternary heavy metal mixture-induced impairments in albino Sprague Dawley rats.

Keywords: Beneficial effects of Zn and Se; Cerebellum; Cerebral cortex; Heavy metals mixture.