Green-synthesized selenium-hydroxytyrosol nanocomposites attenuate hepatocellular carcinoma in rats by modulating oxidative stress, inflammation, and apoptosis.

Hepatocellular carcinoma (HCC) poses a significant health risk and greatly affects global rates of illness and death, highlighting an urgent requirement for new treatment strategies. This study examines the therapeutic effects of selenium-hydroxytyrosol nanocomposites (Se-HTNPs) in a rat model with HCC caused by diethylnitrosamine (DEN). Treatment with Se-HTNPs significantly inhibited serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin, while increasing serum albumin and total protein levels. Oxidative stress was alleviated, as evidenced by a marked reduction in hepatic malondialdehyde (MDA) levels and an increase in antioxidant markers, such as reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC). Se-HTNPs also significantly decreased hepatic inflammatory markers, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), as well as apoptotic markers (p53 and caspase-3) and vascular endothelial growth factor (VEGF). Furthermore, Se-HTNPs suppressed the mRNA expression of c-Jun N-terminal kinase (c-JNK) and nuclear factor kappa B (NF-κB) and improved histopathological alterations brought on by DEN. These findings suggest that Se-HTNPs mitigate DEN-induced HCC in rats through their potent antioxidant, anti-inflammatory, and anti-carcinogenic properties, underscoring their potential as a therapeutic strategy for HCC.