Total saponins from ginseng stems and leaves antagonise acute lead-cadmium co-exposure-induced oxidative liver damage in mice via the Keap1/Nrf2 signalling pathway.

1. Lead (Pb) and cadmium (Cd) induce liver damage mainly via oxidative stress. Total saponins from ginseng stems and leaves (TSGSL) possess antioxidant properties, but their protective effect against Pb-Cd co-exposure remains unclear.2. This study aimed to investigate the hepatoprotective effect and mechanism of TSGSL in acute Pb-Cd co-exposed mice.3. Male KM mice received TSGSL (30 or 60 mg/kg, orally) once daily for 14 days, then a single acute exposure to Pb (150 mg/kg) and Cd (15 mg/kg). Liver function, oxidative stress markers, histopathology, pro-inflammatory cytokines, and Keap1/Nrf2 pathway gene mRNA were assessed.4. TSGSL dose-dependently alleviated Pb-Cd-induced liver injury. At 60 mg/kg, it reduced ALT by 46.0% and AST by 43.3%, decreased hepatic MDA by 50.0%, increased hepatic T-SOD, CAT and GSH-PX by 36.9%, 69.5% and 36.7%, respectively, and lowered pro-inflammatory cytokines (e.g. TNF-α by 51.7% and IL-1β by 46.0%). Histopathological damage was ameliorated. TSGSL upregulated mRNA expression of Keap1/Nrf2-related genes. The 30 mg/kg dose showed weaker effects.5. TSGSL protects against acute Pb-Cd-induced oxidative liver damage in mice, potentially via transcriptional upregulation of the Keap1/Nrf2 pathway and enhancement of antioxidant capacity. Further studies are needed to investigate chronic Pb-Cd co-exposure and gut microbiota involvement.