Chrysin-loaded poly (lactic-co-glycolic acid) nanoparticles alleviate sepsis-induced splenic injury by regulating myeloid-derived suppressor cells.

Abstract

Sepsis is a serious condition resulting from a dysregulated immune-mediated response to an infection. Myeloid-derived suppressor cells (MDSCs) aggregate and serve a protective function in the pathophysiology of lipopolysaccharide (LPS) shock. However, the regulation of MDSCs by chrysin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (CHR-NP) remains unexplored. CHR-NP was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS). Before being given an intraperitoneal injection of 10 mg/kg of LPS, C57BL/6 mice were given CHR (50 mg/kg), PLGA (50 mg/kg), CHR-NP (50 mg/kg), and dexamethasone (Dexa) (5 mg/kg) by oral administration for 6 days. CHR-NP effectively mitigated LPS-induced splenic injury by diminishing inflammation and oxidative stress. The CHR-NP treatment lowered the amount of malondialdehyde (MDA) and raised the levels of antioxidants like glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx). Besides that, it stopped the production of cytokines that cause inflammation (tumor necrosis factor (TNF)-α, IL-1β, interferon (IFN)-γ, and IL-12) and increased the production of cytokines that stop inflammation (IL-10 and IL-4). This study demonstrates that CHR-NPs confer significant protective effects against LPS-induced sepsis by modulating immune responses, reducing oxidative stress, and alleviating splenic injury. The ability of CHR-NP to enhance antioxidant defenses, suppress pro-inflammatory cytokines, and promote anti-inflammatory mediators highlights its potential as a novel therapeutic approach for regulating MDSCs and mitigating sepsis-related immunopathology.