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Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Mechanistic Modulation of Lipopolysaccharide-Induced Hepatic Injury by Chitosan-Coated Selenium Nanoparticles:
Asmaa Ramadan1, Eman Hamza2, Eman Ali Elkordy3
1Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt.
Abstract:
Background/Objectives: The aim of the current study was to investigate the mechanistic hepatoprotective efficacy of selenium (SE) and chitosan-coated selenium nanoparticles (CS-SENPs) using a rat model induced by lipopolysaccharide (LPS). Methods: CS-SENP was prepared and characterized for particle size, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Male albino rats (n = 40) were divided into four groups: control, LPS, SE, and CS-SENP. SE and CS-SENPs (5 mg/kg orally for 14 days) were given before LPS injection. Tissue architecture was assessed using histopathological analysis. HSP-47 and STEAP-3 protein expression levels were measured using ELISA, and oxidative stress markers were quantitatively evaluated. The expression of HO-1, TLR-4, STAT-3, TRAF-6, and IL-17A was measured using immunohistochemical analysis. Furthermore, HSP-90 expression was evaluated by immunofluorescence labeling. Results: CS-SENP characterization revealed uniform (PDI = 0.125 ± 0.04) nanoparticle size (108.54 ± 2.24 nm), with high zeta potential (+63.92 ± 6.287 mV), attributed to the CS layer, which was confirmed by FTIR and TEM as an electron-lucent halo enveloping the individual SENP cores. CS-SENPs significantly reduced lipid peroxidation (MDA) and restored glutathione (GSH) more effectively than SE. CS-SENPs improved redox (upregulated HO-1) and iron balance (downregulated STEAP-3), and also increased the anti-inflammatory effect (suppressed TLR-4, IL-17A, TRAF-6, and STAT-3). CS-SENPs showed superior antifibrotic efficacy (suppresses stress proteins, HSP-47 and HSP-90). Rats treated with CS-SENPs had nearly normal liver structure. Conclusions: The results concluded that CS-SENPs had superior and multi-targeted hepatoprotection against LPS-induced liver damage.
Insights
Chitosan-coated selenium nanoparticles (CS-SENPs) offer superior hepatoprotection against lipopolysaccharide (LPS)-induced liver damage in rats compared to selenium alone. CS-SENPs effectively reduce oxidative stress, inflammation, and fibrosis, restoring normal liver structure.
Area of Science:
- Nanomedicine
- Hepatology
- Toxicology
Background:
- Lipopolysaccharide (LPS) induces significant liver damage.
- Selenium (SE) has known hepatoprotective properties.
- Chitosan-coated selenium nanoparticles (CS-SENPs) offer a novel delivery system for SE.
Purpose of the Study:
- To investigate the mechanistic hepatoprotective efficacy of SE and CS-SENPs.
- To evaluate the effects of CS-SENPs on LPS-induced liver injury in a rat model.
- To compare the efficacy of CS-SENPs with conventional SE treatment.
Main Methods:
- CS-SENPs were synthesized and characterized (particle size, PDI, zeta potential, TEM, FTIR).
- Hepatoprotective effects were assessed in male albino rats exposed to LPS.
- Evaluations included histopathology, ELISA for HSP-47 and STEAP-3, oxidative stress markers, and immunohistochemistry for HO-1, TLR-4, STAT-3, TRAF-6, IL-17A, and HSP-90.
Main Results:
- CS-SENPs exhibited optimal nanoparticle characteristics (108.54 nm size, 0.125 PDI, +63.92 mV zeta potential).
- CS-SENPs significantly reduced lipid peroxidation (MDA), restored glutathione (GSH), upregulated HO-1, and downregulated STEAP-3 more effectively than SE.
- CS-SENPs demonstrated superior anti-inflammatory (suppressed TLR-4, IL-17A, TRAF-6, STAT-3) and antifibrotic (suppressed HSP-47, HSP-90) effects, preserving near-normal liver architecture.
Conclusions:
- CS-SENPs provide superior and multi-targeted hepatoprotection against LPS-induced liver damage.
- The enhanced efficacy is attributed to improved redox and iron balance, potent anti-inflammatory actions, and antifibrotic properties.
- CS-SENPs represent a promising therapeutic strategy for liver injury.
