6-Gingerol inhibition of NF-kB expression in diethylnitrosamine initiated, 2-acetylaminofluorene-promoted liver dysfunction and inflammation involves induction of antioxidant enzymes and suppression of pro-inflammatory cytokines

This study investigates the hepatoprotective effects of [6]-gingerol against liver dysfunction and inflammation induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in mice. BALB/c mice were divided into four groups and treated with DEN, 2-AAF, [6]-gingerol, or a combination thereof. Biochemical, histological, and immunohistochemical analyses were conducted to evaluate liver function, oxidative stress, and inflammation. Mice exposed to DEN and 2-AAF exhibited significant hepatic injury, characterized by elevated serum liver enzymes (ALT, AST, ALP, γ-GT), reduced antioxidant enzyme activities (SOD, CAT, GPx, GST), increased lipid peroxidation, nitric oxide production, and expression of pro-inflammatory markers (NF-κB, iNOS, COX-2). Histopathological examination confirmed substantial liver damage. Pre-treatment with [6]-gingerol significantly mitigated these effects, restoring antioxidant enzyme activities, reducing oxidative and nitrosative stress, and suppressing the expression of inflammatory mediators. Liver histoarchitecture also improved markedly in [6]-gingerol-pretreated mice. These findings suggest that [6]-gingerol confers protective effects via antioxidant and anti-inflammatory mechanisms, primarily through modulation of the NF-κB signaling pathway. The results highlight the therapeutic potential of [6]-gingerol in preventing liver diseases associated with xenobiotic-induced oxidative stress and inflammation.