Abstract

PLUMBAGIN AND GRISEOFULVIN MITIGATE NDEA-INDUCED HEPATIC DAMAGE IN MICE

Ekta Tyagi, Rajabrata Bhuyan*, Anand Prakash*

Abstract

Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. N-nitrosodiethylamine (NDEA), a potent environmental carcinogen, plays a key role in liver tumorigenesis. Natural compounds such as plumbagin and griseofulvin have demonstrated anticancer properties in various preclinical models but remain underexplored in liver cancer. Objective This study investigates the protective effects of plumbagin and griseofulvin against NDEA-induced hepatic toxicity and genotoxicity in Swiss albino mice, using sorafenib as a reference compound. Methods Male Swiss albino mice were randomly divided into seven groups (n=6). Acute hepatotoxicity was induced via oral NDEA (200 mg/kg), followed by treatment with low and high doses of plumbagin (2 and 6 mg/kg, i.p.), griseofulvin (225 and 450 mg/kg, oral), and sorafenib (30 mg/kg, oral). Morphological, behavioral, physiological, and genomic parameters were monitored. DNA damage was evaluated using the alkaline Comet assay. Results NDEA exposure led to significant body weight loss, liver enlargement, behavioral alterations, and severe genotoxicity. Treatment with plumbagin and griseofulvin reversed these effects in a dose-dependent manner. High doses of both compounds significantly reduced tail DNA percentage, tail moment, and olive tail moment (p < 0.05), comparable to or exceeding sorafenib efficacy. Conclusion Plumbagin and griseofulvin exert genoprotective and hepatorestorative effects in NDEA-induced liver toxicity. These findings support their potential as anticancer agent for liver cancer.

Keywords: Hepatocellular carcinoma, Genotoxicity and hepatoprotection, N nitrosodiethylamine (NDEA).