Selenium Protects Against Cadmium-Induced Hepatotoxicity via Regulation of Lipid Metabolism and Inflammatory Pathways

Cadmium (Cd), a widespread environmental pollutant, poses significant risks to human health due to its high bioaccumulation potential and prolonged biological half-life. Selenium (Se) has been reported to exert protective effects against Cd-induced organ toxicity; however, the underlying molecular mechanisms, particularly those associated with lipid metabolism and inflammatory regulation, remain insufficiently elucidated.

The hepatoprotective effects of Se, administered as selenomethionine (SeMet) and Se-enriched Cardamine enshiensis extract (CE), were investigated against Cd-induced hepatic injury using both in vitro (L-02 hepatocytes) and in vivo (C57BL/6J mice) models.

SeMet significantly attenuated Cd-induced cytotoxicity, lipid accumulation, and metabolic dysregulation in L-02 cells. In Cd-exposed mice, treatment with SeMet or CE significantly mitigated hepatic injury, steatosis, and inflammation, as evidenced by normalized serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC) levels, improved hepatic histoarchitecture, and reduced lipid droplet deposition. Integrated lipidomic and transcriptomic analyses demonstrated that Se supplementation restored Cd-perturbed polyunsaturated fatty acid metabolism, downregulated lipogenic genes (SCD1, Pparγ, Fasn), and suppressed pro-inflammatory mediators (Cxcl2, Ccl2).

Se confers hepatoprotection against Cd toxicity not only through its classical antioxidant activity but also through coordinated modulation of lipid metabolic pathways and inflammatory signaling. This study provides mechanistic insights into Se-mediated defense against Cd-induced hepatotoxicity and highlights the therapeutic potential of Se-enriched phytochemicals for mitigating the adverse effects of environmental Cd exposure.