Abdelmawgood Islam Ahmed, Badr Abeer Mahmoud, Abdelkader Asmaa Elsayed, Mahana Noha A, Mohamed Ayman Saber, Abdelfattah Hadeer Hesham
Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.
Immunol Res. 2025 May 13;73(1):80. doi: 10.1007/s12026-025-09634-5.
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.
脓毒症是一种因对感染的免疫介导反应失调而导致的严重病症。髓源性抑制细胞（MDSCs）聚集并在脂多糖（LPS）休克的病理生理学中发挥保护作用。然而，载有白杨素的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（CHR-NP）对MDSCs的调节作用仍未得到探索。通过傅里叶变换红外（FTIR）光谱、透射电子显微镜（TEM）、zeta电位和动态光散射（DLS）对CHR-NP进行了合成和表征。在腹腔注射10mg/kg LPS之前，C57BL/6小鼠通过口服给予CHR（50mg/kg）、PLGA（50mg/kg）、CHR-NP（50mg/kg）和地塞米松（Dexa）（5mg/kg），持续6天。CHR-NP通过减轻炎症和氧化应激有效减轻了LPS诱导的脾脏损伤。CHR-NP治疗降低了丙二醛（MDA）的含量，并提高了谷胱甘肽（GSH）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）等抗氧化剂水平。除此之外，它还抑制了促炎细胞因子（肿瘤坏死因子（TNF）-α、白细胞介素-1β、干扰素（IFN）-γ和白细胞介素-12）的产生，并增加了抗炎细胞因子（白细胞介素-10和白细胞介素-4）的产生。本研究表明，CHR-NP通过调节免疫反应、降低氧化应激和减轻脾脏损伤，对LPS诱导的脓毒症具有显著的保护作用。CHR-NP增强抗氧化防御、抑制促炎细胞因子和促进抗炎介质的能力突出了其作为调节MDSCs和减轻脓毒症相关免疫病理学的新型治疗方法的潜力。
