Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.
Biochim Biophys Acta. 2018 Apr 12. Epub 2018 Apr 12. PMID: 29656123
BACKGROUND: The protective effect of selenium (Se) on cadmium (Cd) toxicity is well documented, but underlying mechanisms are unclear.
METHODS: Male mice fed standard diet were given Cd (CdCl, 18 μmol/L) in drinking water with or without Se (NaSeO20 μmol/L) for 16 weeks. Lungs were analyzed for Cd concentration, transcriptomics and metabolomics. Data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study.
RESULTS: Mice treated with Cd had higher lung Cd content (1.7 ± 0.4 pmol/mg protein) than control mice (0.8 ± 0.3 pmol/mg protein) or mice treated with Cd and Se (0.4 ± 0.1 pmol/mg protein). Gene set enrichment analysis of transcriptomics data showed that Se prevented Cd effects on inflammatory and myogenesis genes and diminished Cd effects on several other pathways. Similarly, Se prevented Cd-disrupted metabolic pathways in amino acid metabolism and urea cycle. Integrated transcriptome and metabolome network analysis showed that Cd treatment had a network structure with fewer gene-metabolite clusters compared to control. Centralitymeasurements showed that Se counteracted changes in a group of Cd-responsive genes including Zdhhc11, (protein-cysteine S-palmitoyltransferase), Ighg1 (immunoglobulin heavy constant gamma-1) and associated changes in metabolite concentrations.
CONCLUSION: Co-administration of Se with Cd prevented Cd increase in lung and prevented Cd-associated pathway and network responses of the transcriptome and metabolome. Se protection against Cd toxicity in lung involves complex systems responses.
GENERAL SIGNIFICANCE: Environmental Cd stimulates proinflammatory and profibrotic signaling. The present results indicate that dietary or supplemental Se could be useful to mitigate Cd toxicity.