Biosynthesized Selenium-hydroxytyrosol nanoparticles attenuate hepatocellular carcinoma in rats

Hepatocellular carcinoma (HCC) is a life-threatening disease with a global impact, underscoring the urgent need for the development of new therapeutic agents. This study evaluates the therapeutic effect of selenium-hydroxytyrosol nanoparticles (Se-HTNPs) in a rat model of HCC induced by diethylnitrosamine (DEN). In vitro, Se-HTNPs treatment reduced the viability of Hep G2 cells in a dose-dependent manner, with an IC ₅₀ value of 61.29 ± 1.12 µg/mL. The results confirmed the antioxidant, anti-inflammatory, and anti-carcinogenic properties of Se-HTNPs, demonstrating their effectiveness against DEN-induced HCC. The therapeutic effects of Se-HTNPs were validated by inhibiting serum ALT, AST, and ALP enzyme activities and reducing serum total bilirubin levels. Simultaneously, Se-HTNPs enhanced serum albumin and total protein levels. Additionally, Se-HTNPs alleviated oxidative stress by significantly lowering hepatic lipid peroxidation (MDA) levels and markedly increasing antioxidant marker levels (GSH, SOD, and TAC) compared to DEN-administered rats. Se-HTNPs also significantly reduced hepatic inflammatory markers (TNFα, IL-6, and IL-1β), apoptotic markers (p53 and caspase 3), and VEGF levels. Furthermore, compared to the DEN group, Se-HTNPs distinctly suppressed c-JNK mRNA and NF-κB mRNA gene expression levels. Moreover, Se-HTNP treatment significantly improved the histological alterations induced by DEN. In conclusion, these findings suggest that Se-HTNPs mitigate DEN-induced HCC in rats through their potent antioxidant, anti-inflammatory, and anti-carcinogenic properties.