Evaluation of anticancer activity of beta glucan in non-alcoholic steatohepatitis associated hepatocellular carcinoma in rats.

BACKGROUND: Hepatocellular carcinoma (HCC) arising from non-alcoholic steatohepatitis (NASH) represents a growing clinical challenge with limited therapeutic options. Despite known antioxidant and immunomodulatory properties, the role of beta-glucan in NASH-associated HCC remains insufficiently explored.

METHODS: HCC was experimentally induced in rats via a single intraperitoneal (i.p.) injection of diethylnitrosamine (DEN; 200 mg/kg), followed by repeated intraperitoneal administrations of thioacetamide (TAA; 300 mg/kg) thrice weekly for four weeks. Upon establishment of hepatic tumors, beta-glucan was administered orally (p.o.) at doses of 25, 50, and 75 mg/kg/day for eight consecutive weeks. Sorafenib (30 mg/kg/day; p.o.) was used as the reference standard. Key parameters, including serum biochemical markers, oxidative stress indicators, insulin-like growth factor-1 (IGF-1) levels, and histopathological alterations, were evaluated to assess therapeutic efficacy.

RESULTS: Administration of high-dose beta-glucan (75 mg/kg/day, p.o.) significantly ameliorated hepatic injury, as evidenced by reductions in serum ALT and AST levels, restoration of antioxidant balance (increased GSH and decreased MDA), downregulation of IGF-1 expression, and normalization of hepatic histoarchitecture, demonstrating effects comparable to sorafenib. The intermediate dose (50 mg/kg/day, p.o.) conferred moderate hepatoprotective and anticancer effects, whereas the low dose (25 mg/kg/day, p.o.) exhibited minimal efficacy, with no significant improvements in most evaluated parameters.

CONCLUSION: Beta-glucan exhibits dose-dependent protective effects in a preclinical model of NASH-associated HCC, potentially mediated through antioxidant and growth factor-modulating mechanism. These findings warrant further molecular and clinical investigation.