# Mechanistic Modulation of Lipopolysaccharide-Induced Hepatic Injury by Chitosan-Coated Selenium Nanoparticles: Targeting the STEAP-3/TLR-4 and IL-17/TRAF-6/HSP-90 Axes

## TL;DR

This study shows that chitosan-coated selenium nanoparticles protect the liver from injury caused by a bacterial toxin, better than selenium alone.

## Contribution

The novel contribution is the mechanistic evidence that CS-SENP provides multi-targeted liver protection by modulating specific protein pathways.

## Key findings

- CS-SENP reduced oxidative stress and restored glutathione levels more effectively than selenium alone.
- CS-SENP suppressed pro-inflammatory proteins like TLR-4, IL-17A, and TRAF-6, and downregulated STEAP-3.
- CS-SENP improved liver structure and reduced fibrosis markers like HSP-47 and HSP-90.

## 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.