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

Abstract

Objective: 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 (CCl4)-induced liver injury in Swiss albino mice. Methods: Biogenic silver nanoparticles were synthesized from β-sitosterol to produce β-sitosterol (BS) conjugated silver nanoparticles. Serum liver function assays in mice model with CCl4-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. Results: 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 CCl4 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 CCl4 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. Conclusion: 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.

Keywords

• BSAgNPs
• Hepatotoxicity
• Oxidative stress
• Liver fibrosis
• Nrf2
• TGF-β