Ganoderma atrum polysaccharides attenuates cadmium mediated hepatorenal dysfunction, oxidative stress, inflammation response, and metabolic disorders in mice.

Cadmium (Cd), a prevalent environmental contaminant, has raised significant public health concerns. Previous studies have demonstrated the effective free radical scavenging capacity of Ganoderma atrum polysaccharides (GAP), though its potential protective effects against Cd-induced toxicity remain unexplored. This study established a mice model to evaluate the hepatorenal protective efficacy of GAP against chronic Cd exposure. Mice were randomly divided into three groups: Control, Model (Cd 5 mg/kg), and GAP treatment (Cd 5 mg/kg + GAP 200 mg/kg) for 28 consecutive days. Our findings revealed that Cd exposure induced significant hepatorenal dysfunction, oxidative stress imbalance, and systemic metabolic disturbances. Notably, GAP supplementation effectively restored serum biomarkers of hepatic and renal injury (ALT, AST, CR, and BUN) to near-normal levels. The polysaccharide demonstrated remarkable antioxidant capacity by reversing Cd-induced depletion of catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD), while significantly reducing malondialdehyde (MDA) content. Mechanistic investigations revealed GAP's anti-inflammatory potential through downregulation of TLR4/MyD88/NF-κB signaling pathway components. Untargeted metabolomics analysis further indicated that GAP administration ameliorated Cd-induced metabolic dysregulation, particularly in colonic metabolites. These comprehensive results substantiate that GAP confers multi-organ protection against Cd toxicity through coordinated antioxidant, anti-inflammatory, and metabolic regulatory mechanisms, highlighting its potential as a natural detoxification agent against heavy metal exposure.