Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1.

ABSTRACT

Cadmium (Cd) is a hazardous environmental metal that poses a global public health concern due to its high toxic potential. Nanoselenium (Nano-Se) is a nanoform of elemental Se that is widely used to antagonize heavy metal toxicity owing to its high safety margin with low doses. However, the role of Nano-Se in relieving Cd-induced brain damage is unclear. For this study, Cd-exposure-induced cerebral damage was established by using a chicken model. Administration of Nano-Se with Cd significantly decreased the Cd-mediated elevation of cerebral ROS, MDA, and H2O2 levels as well as markedly increased the Cd-mediated reduced activities of antioxidant biomarkers (GPX, T-SOD, CAT, and T-AOC). Accordingly, co-treatment with Nano-Se significantly reduced Cd-mediated increased Cd accumulation and recovered the Cd-induced biometal imbalance, notably Se and Zn. Nano-Se downregulated the Cd-induced upregulation of ZIP8, ZIP10, ZNT3, ZNT5, and ZNT6 and upregulated the Cd-mediated decreased expressions of ATOX1 and XIAP. Nano-Se also increased the Cd-mediated decreased mRNA levels of MTF1 and its target genes MT1 and MT2. Surprisingly, co-treatment with Nano-Se regulated the Cd-induced increased total protein level of MTF1 by reducing its expression. Moreover, altered selenoproteins regulation was recovered after co-treatment with Nano-Se as evidenced by increased expression levels of antioxidant selenoproteins (GPx1-4 and SelW) and Se transport-related selenoproteins (SepP1 and SepP2). The histopathological evaluation and Nissl staining of the cerebral tissues also supported that Nano-Se markedly reduced the Cd-induced microstructural alterations and well preserved the normal histological architectures of the cerebral tissue. Overall, the results of this research reveal that Nano-Se may be beneficial in mitigating Cd-induced cerebral injury in the brains of chickens. This present study provides a basis for preclinical research for its usefulness as a potential therapeutic for the treatment of neurodegeneration in the heavy-metal-induced neurotoxicity.