Selenium ameliorates mercuric chloride-induced brain damage through activating BDNF/TrKB/PI3K/AKT and inhibiting NF-κB signaling pathways

Abstract

Mercuric chloride (HgCl₂), a heavy metal compound, causes neurotoxicity of animals and humans. Selenium (Se) antagonizes heavy metal-induced organ damage with the properties of anti-oxidation and anti-inflammation. Nevertheless, the molecular mechanism underlying the protective effects of sodium selenite (Na₂SeO₃) against HgCl₂-induced neurotoxicity remains obscure. Therefore, the present study aimed to explore the protective mechanism of Na₂SeO₃ on HgCl₂-induced brain damage in chickens. Morphological observations showed that Na₂SeO₃ alleviated HgCl₂-induced brain tissues damage. The results also showed that Na₂SeO₃ decreased the protein expression of S100 calcium binding protein B (S100B), and increased the levels of nerve growth factors (NGF), doublecortin domain containing 2 (DCDC2), as well as neurotransmitter to reverse HgCl₂-induced brain dysfunction. Further, Na₂SeO₃ attenuated HgCl₂-induced oxidative stress by decreasing the level of malondialdehyde (MDA) and increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). Mechanistically, Na₂SeO₃ activated the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor type B (TrKB)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and suppressed the nuclear factor kappa B (NF-κB) signaling pathway to inhibit apoptosis and inflammation caused by HgCl₂ exposure. In summary, Na₂SeO₃ ameliorated HgCl₂-induced brain injury via inhibiting apoptosis and inflammation through activating BDNF/TrKB/PI3K/AKT and suppressing NF-κB pathways.

Keywords: Apoptosis; Brain; Chicken; Inflammation; Mercuric chloride; Na(2)SeO(3).