Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox imbalance, Bax/Bcl-2 and NF-kB signaling pathways in male rats

Aim of this study was to investigate the efficacy ofGinkgo Biloba(G.B) hydro-ethanolic extract against hepatotoxicity induced by combined exposure to cadmium (Cd) and fluoride (F) in Wistar rats. Animals were exposed to F (30 mg/L) + Cd (40 mg/L), F + Cd plus G.B (50,100 and 200 mg/kg), G.B (200 mg/kg), F + Cd plus Vit C(1000 mg/L) in drinking water for 42 days. Significant raise in liver enzymes and histopathological changes were observed in F + Cd treated rats. F + Cd exposure enhanced protein and glutathione oxidation, lipid peroxidation and decreased superoxide dismutase activity. F and Cd combination also caused mitochondrial dysfunction, swelling and mitochondrial membrane potential collapse in liver isolated mitochondria. Up-regulation of inflammatory genes (TNF-alpha, IL-1 beta and NF-kB) and pro-apoptotic Bax as well as down-regulation of anti-apoptotic Bcl-2 were detected after co-exposure to F and Cd. Interestingly, G.B alleviated F + Cd induced liver oxidative stress, mitochondrial damage and prevented inflammation and apoptosis. Furthermore, decrease in serum liver enzymes and improvement of histopathologic lesions were observed in G.B treated rats. This study explored the potential beneficial role of G.B on F + Cd combined hepatotoxic effects via considering its possible antioxidant, anti-inflammatory, mitochondrial protection and anti-apoptotic effects. Keywords:Ginkgo biloba; Cadmium; Fluoride; Oxidative stress; Inflammation; Mitochondrial apoptosi