Anti-cancer, anti-inflammatory and antioxidant effects of Vit-A/C@SeNPs in mutual diethylnitrosamine and carbon tetrachloride induced hepatocellular damage in albino rats

Abstract

The purpose of this research was to create a nano-platform containing selenium, vitamin C, and vitamin A (Vit-A/C@SeNPs) as a potential preventive and curative agent against hepatocellular cancer. Transmission electron microscope (TEM), dynamic light scattering (DLS) and UV–visible spectroscopy were used to characterize Vit A/C@SeNPs, and the zeta potential was evaluated to assess their stability. To determine its antioxidant capacity and cytotoxicity; the DPPH (2,2diphenyl-1-picryl-hydrazyl-hydrate) and the sulforhodamine B (SRB) assay were used. For additional in-vivo pharmacokinetic investigations on normal murine, 99mTc-Vit-A/C@SeNPs were radio-synthesized using technetium-99 m. For studying the anti-inflammatory, anti-cancer, and antioxidant effect of this nano-platform in-vivo, Wistar Albino rats suffered hepatocellular damage, induced by N-diethyl nitrosamine (DEN)/carbon tetrachloride (CCl4) administration to produce inflammation and fibrosis in rats, were used. The synthesis provided Vit-A/C@SeNPs with a spherical shape, 70–80 nm average size range, a radical scavenging activity of 60.23% at a concentration of 1 mg/mL, IC50 of 25.6 μg/mL, and −15mV for zetapotential. According to the biochemical analysis results, after administration of Vit-A/C@SeNPs as a liver therapeutic or preventive drug, show distinguishable lowering in liver biochemical marker values such as Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), γ-Glutamyltransferase (GGT), T. bilirubin and Alkaline phosphatase (ALP), as well as remarkable depletion of L-malondialdehyde (L-MDA) in liver, with increase of catalase (CAT) activity & glutathione-S-transferase (GST) conc., and apparent amelioration in the histopathological examination of liver tissue samples. Quantitative real-time polymerase chain reaction (qPCR) for mRNA gene expression levels of inflammatory genes (TGF-β1, NF-κB, PPAR-γ, iNOS & TNFα) and P53 (cellular tumor suppressor gene) revealed a substantial up-regulation. The results were pertinent to damage and inflammation in hepatic cells histopathology, values dropped and tends to normal in both treatment & prevention groups. Interestingly, Vit-A/C@SeNPs usage for treatment or prevention, had showed a significant histological feature improvement in liver tissue.