Rutin-biosynthesized selenium nanoparticles mitigate 5-fluorouracil induced neurotoxicity via modulation of the ROS/Nrf2/NF-κB mitochondrial apoptosis axis
Salah S. Elyan , Moaz Elsayed , Nesreen ashraf , Nada Sayed , Mohamed Saleh , Madonna Osama , Sama Ahmed , Mohamed H.A. Gadelmawla , Khaled M. Alam-ElDein
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引用次数: 0
Abstract
5-Fluorouracil (5-FU) is an effective chemotherapeutic agent, but its use is often limited by neurotoxic side effects. This study evaluated the neuroprotective effects of rutin (RUT), sodium selenite (Na₂SeO₃), and rutin-stabilized selenium nanoparticles (RUT-SeNPs) against 5-FU-induced neurotoxicity in rats. The animals were divided into five groups: control, 5-FU, 5-FU&Na₂SeO₃, 5-FU&RUT, and 5-FU&RUT-SeNPs. 5-FU administration caused significant neurotoxicity, including increased oxidative stress (MDA: 178.3%, NO: 146.29%), inflammatory cytokine levels (TNF-α: 196.14%, IL-6: 300.67%), and apoptotic markers (Bax: 119.43%, Caspase-3: 191.25%), and decreased neurotrophic factors and activation of astrocyte (BDNF: −51.29%, GFAP: 224.52%). Treatment with RUT-SeNPs showed the strongest neuroprotective effect, significantly reducing oxidative stress (MDA: −64.44%, NO: −50.71%), inflammatory markers (TNF-α: −60.27%, IL-6: −75.56%), and apoptotic indicators (Bax: −48.30%, Caspase-3: −56.74%). RUT-SeNPs treatment also significantly improved neurotrophic factor levels and astrocyte suppression (BDNF: 121.01%, GFAP: −60.63%) and restored Nrf2 expression (104.34%) and NF-kB levels (53.40%) to near-normal levels, as evidenced by histopathological and immunohistochemical findings. These results suggest that RUT-SeNPs offer superior neuroprotection compared to free rutin and sodium selenite and may serve as a promising adjunct to mitigate 5-FU-induced neurotoxicity.
期刊介绍:
Nano-Structures & Nano-Objects is a new journal devoted to all aspects of the synthesis and the properties of this new flourishing domain. The journal is devoted to novel architectures at the nano-level with an emphasis on new synthesis and characterization methods. The journal is focused on the objects rather than on their applications. However, the research for new applications of original nano-structures & nano-objects in various fields such as nano-electronics, energy conversion, catalysis, drug delivery and nano-medicine is also welcome. The scope of Nano-Structures & Nano-Objects involves: -Metal and alloy nanoparticles with complex nanostructures such as shape control, core-shell and dumbells -Oxide nanoparticles and nanostructures, with complex oxide/metal, oxide/surface and oxide /organic interfaces -Inorganic semi-conducting nanoparticles (quantum dots) with an emphasis on new phases, structures, shapes and complexity -Nanostructures involving molecular inorganic species such as nanoparticles of coordination compounds, molecular magnets, spin transition nanoparticles etc. or organic nano-objects, in particular for molecular electronics -Nanostructured materials such as nano-MOFs and nano-zeolites -Hetero-junctions between molecules and nano-objects, between different nano-objects & nanostructures or between nano-objects & nanostructures and surfaces -Methods of characterization specific of the nano size or adapted for the nano size such as X-ray and neutron scattering, light scattering, NMR, Raman, Plasmonics, near field microscopies, various TEM and SEM techniques, magnetic studies, etc .