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Green-Synthesized Rutin-Capped Gold Nanoparticles Attenuate Experimental Liver Fibrosis by Targeting Oxidative Stress
Roxana Maria Decea1, Ioana Baldea1, Gabriela Adriana Filip2
1Department of Physiology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Clinicilor 1, 400006 Cluj-Napoca, Romania.
None:
Liver fibrosis is driven by persistent oxidative stress and inflammatory signaling, with transforming growth factor-β (TGF-β) acting as a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but its low bioavailability limits therapeutic efficacy. This study investigated whether rutin-phytoreduced gold nanoparticles (RuAuNPs) enhanced rutin delivery leading to antifibrotic and anti-inflammatory effects in a rat model of liver fibrosis. Liver fibrosis was induced by oral administration of thioacetamide (TAA, 150 mg/kg body weight, p.o.) for six weeks. Following fibrosis induction, the animals were treated with free rutin (30 mg/kg body weight), RuAuNPs (0.3 mg/kg body weight), or AuNPs (0.3 mg/kg body weight), both expressed as nanoparticle mass, all administered orally for four weeks. RuAuNPs were synthesized by green rutin-mediated reduction and further characterized by TEM, DLS, and FTIR spectroscopy; they were spherical, showing an average hydrodynamic size of 104.1 nm (PDI 0.345). FTIR confirmed rutin capping. Biological effects were evaluated by liver morphology (H&E histology, TEM), biochemical assessment of liver aminotransferases and glico-lipidic status, ELISA and spectrophotometry measurement of redox biomarkers (lipid peroxidation, glutathione status, antioxidant enzymes), cytokines (TNF-α, IL-1β, IL-6), and TGF-β. TAA-induced hepatic injury and remodeling with increased profibrotic signaling, oxidative stress, and inflammation. Free rutin slightly ameliorated the liver damage, whereas RuAuNP improved histological features, reduced TGF-β and pro-inflammatory cytokines, decreased lipid peroxidation, and supported antioxidant defenses. Overall, RuAuNP may enhance rutin efficacy in TAA-induced liver fibrosis, with novelty stemming from the integrated in vivo evaluation of tissue changes and key profibrotic/oxidative/inflammatory pathway.
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