Cytoprotection against Cadmium by Nrf2-Activating Dietary Phytochemicals.

Background: Environmental exposure to toxic heavy metals such as cadmium continues to cause significant human health impacts around the world. Objective: This aim of this study was to determine potential benefits of a Nrf2 activating phytochemical combination against cadmium-induced cytotoxicity. Methods: Human Hepatocellular Carcinoma (HepG2) cells were treated with the Nrf2-activating PB123 combination of dietary phytochemicals and the cultured HepG2 cells were challenged with cadmium (CdSO4). Cytotoxicity effects were evaluated by assays of cell viability (CCK8 assay) and cell injury (LDH release assay). Gene mRNA expression in PB123-treated cells was determined by RNA-seq. Results: PB123 upregulated metallothionein gene expression in the HepG2 cells, and pretreatment with PB123 protected HepG2 cells from Cd2+ toxicity measured both as cell viability (CCK8 assay) and cell injury (LDH release assay). Use of the Nrf2-inhibitor AEM1 suggested a Nrf2-dependence of the PB123-induced protection. Transcriptomic analyses of gene expression data from PB123-treated cells revealed both Nrf2-related and metallothionein-related pathways as key Reactome findings, and Detoxification as a primary Gene Ontology endpoint. Conclusion: In context with previous work by others, the present findings indicate that rosemary-based dietary supplement products like PB123 might promote beneficial responses against environmental cadmium exposure.