Efficiency of griseofulvin and plumbagin in mitigating N-nitrosodiethylamine-induced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a globally prevalent malignancy often triggered by oxidative stress and exposure to hepatotoxic agents such as N-nitrosodiethylamine (NDEA), which induces DNA adducts, inflammation, and liver dysfunction. Natural compounds like plumbagin (PL) and griseofulvin (GF) have demonstrated anticancer potential; however, their in vivo efficacy in NDEA-induced HCC models remains insufficiently explored. This study investigated the protective effects of PL and GF against NDEA-induced hepatocarcinogenesis in male Swiss albino mice. Animals were randomly assigned to seven groups, including normal control, NDEA control (200 mg/kg), and treatment groups receiving PL (2 mg/kg and 6 mg/kg, intraperitoneally), GF (225 mg/kg and 450 mg/kg, orally), or the reference drug sorafenib (30 mg/kg, orally) for 14 days. Biochemical, hematological, and oxidative stress markers were evaluated alongside histopathological analysis. NDEA exposure significantly elevated liver enzymes (ALT, AST, ALP), cholesterol, and malondialdehyde (MDA), while reducing antioxidant enzyme levels (SOD, CAT, GST, and GSH-Px), indicating marked hepatic damage. Treatment with PL and GF led to significant, dose-dependent restoration of these parameters, with notable reductions in MDA and improvements in antioxidant activity. Histopathological assessments further confirmed these findings, showing reduced fibrosis, enhanced hepatocyte regeneration, and improved liver architecture, particularly with high-dose PL, which demonstrated efficacy comparable to sorafenib. In conclusion, PL and GF exhibited substantial hepatoprotective and anticancer effects in the NDEA-induced HCC model, primarily by restoring liver function, reducing oxidative stress, and improving histological outcomes. These findings support their potential as complementary therapeutic agents in liver cancer management.