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

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 (ZnCl(2); 0.80 mg/kg), sodium selenite (Na(2)SeO(3);1.50 mg/kg) and zinc chloride plus sodium selenite (ZnCl(0.2) + Na(2)SeO(3)) 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.