Quercetin-Functionalized Magnetite Nanoparticles Attenuate Oxidative Stress and Histopathology in DEN-Driven Hepatic Cancer

Abstract

Background: Hepatic cancer remains a clinical challenge, with oxidative stress contributing to tumor progression and tissue remodeling. We evaluated whether quercetin delivered via magnetite nanoparticles (Q-MNPs) can modulate hepatic redox balance and improve liver histology in a diethylnitrosamine (DEN)–induced rat model. Methods: Male rats were allocated to (i) control, (ii) DEN-induced cancer, and (iii) DEN plus Q-MNP treatment. Quercetin was conjugated to magnetite nanoparticles to enhance bioavailability and cellular uptake. After a defined treatment period, hepatic tissue was assayed for lipid peroxidation (malondialdehyde, MDA) and antioxidant defenses (superoxide dismutase, SOD; catalase). Histopathological evaluation assessed tumor burden, fibrosis, inflammation, and biliary reaction. Data are presented as mean ± SEM; group comparisons employed appropriate statistical tests with significance set at p<0.05. Results: DEN exposure markedly increased hepatic MDA, indicating augmented lipid peroxidation and membrane damage. Q-MNPs significantly reduced MDA levels, reflecting attenuation of ROS-mediated lipid injury. Endogenous antioxidant defenses, notably SOD and catalase activities, were disrupted in cancer livers; Q-MNP treatment restored these activities toward control values, suggesting improved dismutation of superoxide and breakdown of hydrogen peroxide. Redox homeostasis shifted from a pro-oxidant to a more balanced state with Q-MNPs, potentially impacting cellular signaling, apoptosis, and the tumor
microenvironment. Histopathology revealed substantial DEN-induced nodular transformations and lobular disarray, which were mitigated by Q-MNPs, evidenced by fewer and smaller nodules and preserved architecture. Fibrosis and inflammatory infiltration were attenuated with Q-MNP treatment, implying reduced stellate cell activation and inflammatory cascades. A milder biliary ductular
response accompanied improved tissue integrity, aligning with reduced cholestatic-like changes. Conclusion: Q-MNPs modulate hepatic redox balance and ameliorate DEN-driven histopathology, supporting their potential as redox-modulating adjuvant therapy to complement conventional hepatic cancer management. Further studies are warranted to define dosing, safety, and translational relevance.