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Abstract

Background: Hepatocellular carcinoma (HCC) is considered a major cause of cancer-related mortality worldwide, which is resistant to several anticancer treatments. Associated with oxidative stress and reduced apoptotic regulation. Garlic displays powerful antioxidant effects and anti-tumor potential. In this study, we investigated the chemo preventive and therapeutic effectiveness of a novel garlic/ZnO/CTAB nanoparticles against diethyl nitrosamine (DEN)-induced hepatocarcinoma, focusing on their influence on cell cycle dynamics and apoptosis. Methods: Sixty male Wistar rats were divided into six groups: normal control, garlic nanoparticles normal-treated, DEN control, DEN + garlic nanoparticle protected, DEN + garlic nanoparticle treated, and DEN + doxorubicin treated as a reference group. In vitro cytotoxicity was assessed in HepG2 cells. In vivo Liver oxidative stress markers (CAT, SOD, GPx, GST, GSH), serum alpha-fetoprotein (AFP), and cell cycle analysis via flow cytometry. Results: DEN exposure significantly increased AFP levels, suppressed antioxidant enzyme activity, and disrupted cell cycle regulation, marked by an increased sub-G0 population and reduced G2/M phase. Both preventive and therapeutic administration of the garlic/ZnO/CTAB nanocomposite effectively reversed these alterations, restoring antioxidant defenses, elevating GSH, decreasing AFP, and normalizing cell cycle distribution. Enhanced apoptotic activity was indicated by G1 phase arrest and a reduced sub-G0 population. Conclusion: Garlic/ZnO/CTAB nanoparticles show strong antioxidant, hepatoprotective, and pro-apoptotic effects against hepatocellular carcinoma. It has great effect in the modulation of oxidative stress and restoration of cell cycle balance.

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