β-sitosterol conjugated silver nanoparticle-mediated amelioration of CCl4-induced liver injury in swiss albino mice

Drug induced hepatocyte death is a major contributor to acute liver failure. We aimed to determine whether β-sitosterol conjugated silver nanoparticles (BSAgNPs) could ameliorate carbon tetrachloride (CCl 4 )-induced liver injury in Swiss albino mice. Biogenic silver nanoparticles were synthesized from β-sitosterol to produce β-sitosterol (BS) conjugated silver nanoparticles. Serum liver function assays in mice model with CCl 4 -induced liver injury revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and cholesterol levels decreased markedly after treatment with β-sitosterol and BSAgNPs. In vivo liver enzymatic assays, including superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were conducted to assess the antioxidant activity of the treatments. Liver tissue from BSAgNP treated mice displayed significantly elevated SOD activity (73.57 ± 1.48%) when compared to positive control group with silymarin treatment. Catalase activity decreased drastically in CCl 4 treated mice (47.14 ± 1.08%), but increased with the administration of BSAgNPs (72.24 ± 2.25%). An increase in transforming growth factor β (TGF-β1) in liver tissue homogenate accompanied a reduction in nuclear factor erythroid-2-related factor 2 (Nrf2) in CCl 4 treated mice. β-sitosterol and BSAgNPs mediated the reduction of TGF-β1. In the BSAgNPs treated mice, Nrf2 level was significantly elevated; however, no change was detected following β-sitosterol treatment. Our findings reveal that β-sitosterol conjugated silver nanoparticles (BSAgNPs) may cause activation of the Nrf2 gene, through potential inhibition of TGF β1/Smad signaling. Antifibrotic effect of BSAgNPs may promote the lowering of chronic inflammation, oxidative stress and collagen deposition. Nanoparticle-mediated drug delivery of β-sitosterol may therefore have therapeutic promise against hepatic complications.