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

Cadmium (Cd) is a hazardous environmental metal thatposes a globalpublic health concern due to its high toxic potential. Nanoselenium(Nano-Se) is a nanoform of elemental Se that is widely used to antagonizeheavy metal toxicity owing to its high safety margin with low doses.However, the role of Nano-Se in relieving Cd-induced brain damageis unclear. For this study, Cd-exposure-induced cerebral damage wasestablished by using a chicken model. Administration of Nano-Se withCd significantly decreased the Cd-mediated elevation of cerebral ROS,MDA, and H2O2 levels as well as markedly increasedthe Cd-mediated reduced activities of antioxidant biomarkers (GPX,T-SOD, CAT, and T-AOC). Accordingly, co-treatment with Nano-Se significantlyreduced Cd-mediated increased Cd accumulation and recovered the Cd-inducedbiometal imbalance, notably Se and Zn. Nano-Se downregulated the Cd-inducedupregulation of ZIP8, ZIP10, ZNT3, ZNT5, and ZNT6 and upregulatedthe Cd-mediated decreased expressions of ATOX1 and XIAP. Nano-Se alsoincreased the Cd-mediated decreased mRNA levels of MTF1 and its targetgenes MT1 and MT2. Surprisingly, co-treatment with Nano-Se regulatedthe Cd-induced increased total protein level of MTF1 by reducing itsexpression. Moreover, altered selenoproteins regulation was recoveredafter co-treatment with Nano-Se as evidenced by increased expressionlevels of antioxidant selenoproteins (GPx1-4 and SelW) andSe transport-related selenoproteins (SepP1 and SepP2). The histopathologicalevaluation and Nissl staining of the cerebral tissues also supportedthat Nano-Se markedly reduced the Cd-induced microstructural alterationsand well preserved the normal histological architectures of the cerebraltissue. Overall, the results of this research reveal that Nano-Semay be beneficial in mitigating Cd-induced cerebral injury in thebrains of chickens. This present study provides a basis for preclinicalresearch for its usefulness as a potential therapeutic for the treatmentof neurodegeneration in the heavy-metal-induced neurotoxicity.

Automated summary

Nanoselenium (Nano-Se) plays a positive role in mitigating cadmium-induced brain injury by reducing cadmium accumulation, regulating gene and protein expressions, enhancing antioxidant capacity, and preserving normal tissue structure.