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负载壳聚糖并增强对广泛耐药和耐万古霉素菌株的抗菌、抗氧化及免疫调节活性:体外和体内研究方法

Chitosan-Loaded and Potentiate Antibacterial, Antioxidant, and Immunomodulatory Activities against Extensive Drug-Resistant and Vancomycin-Resistant : In Vitro and In Vivo Approaches.

作者信息

Taha Selwan M, Abd El-Aziz Norhan K, Abdelkhalek Adel, Pet Ioan, Ahmadi Mirela, El-Nabtity Sameh M

机构信息

Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.

Department of Microbiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.

出版信息

Antioxidants (Basel). 2024 Mar 30;13(4):428. doi: 10.3390/antiox13040428.

DOI:10.3390/antiox13040428
PMID:38671876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11047512/
Abstract

Antimicrobial resistance poses considerable issues for current clinical care, so the modified use of antimicrobial agents and public health initiatives, coupled with new antimicrobial approaches, may help to minimize the impact of multidrug-resistant (MDR) bacteria in the future. This study aimed to evaluate the antimicrobial, antioxidant, and immunomodulatory activities of , , and their chitosan nanocomposites against extensive drug-resistant (XDR) and vancomycin-resistant (VRSA) using both in vitro and in vivo assays. The in vitro antimicrobial susceptibilities of and VRSA strains revealed 100% sensitivity to imipenem (100%). All strains were resistant to cefoxitin, cefepime, trimethoprim + sulfamethoxazole, and fosfomycin. However, strains showed a full resistance to cefoxitin, amoxicillin, ampicillin, erythromycin, chloramphenicol, and fosfomycin (100% each). Interestingly, all strains were vancomycin-resistant (MIC = 32-512 μg/mL), and 90% of and strains were XDR. The antimicrobial potential of and nanocomposites with chitosan nanoparticles demonstrated marked inhibitory activities against XDR and VRSA strains with inhibition zones' diameters up to 50 mm and MIC values ranging from 0.125 to 1 μg/mL and 1 to 8 μg/mL, respectively. The results of the in vivo approach in male Sprague Dawley rats revealed that infection with and displayed significant changes in biochemical, hematological, and histopathological findings compared to the negative control group. These values returned to the normal range after treatment by chitosan nanoparticles, either loaded with or . Real-time quantitative polymerase chain reaction (RT-qPCR) findings presented significant upregulation of the relative expression of the gene and downregulation of the gene throughout the experimental period, especially after treatment with chitosan nanoparticles loaded either with or in comparison to the positive control groups. In conclusion, this is the first report suggesting the use of and nanocomposites with chitosan nanoparticles as a promising contender for combating XDR and VRSA infections as well as a manager for inflammatory situations and oxidative stress-related disorders.

摘要

抗菌药物耐药性给当前临床护理带来了诸多问题,因此抗菌药物的改良使用、公共卫生举措以及新的抗菌方法,或许有助于在未来将多重耐药(MDR)细菌的影响降至最低。本研究旨在通过体外和体内试验,评估[具体物质1]、[具体物质2]及其壳聚糖纳米复合材料对广泛耐药(XDR)[细菌名称1]和耐万古霉素[细菌名称2](VRSA)的抗菌、抗氧化和免疫调节活性。[细菌名称1]和VRSA菌株的体外抗菌药敏试验显示,它们对亚胺培南的敏感性为100%。所有[细菌名称1]菌株对头孢西丁、头孢吡肟、甲氧苄啶+磺胺甲恶唑和磷霉素均耐药。然而,[细菌名称2]菌株对头孢西丁、阿莫西林、氨苄西林、红霉素、氯霉素和磷霉素呈现完全耐药(各为100%)。有趣的是,所有[细菌名称2]菌株均耐万古霉素(MIC = 32 - 512μg/mL),且90%的[细菌名称1]和[细菌名称2]菌株为XDR。含壳聚糖纳米颗粒的[具体物质1]和[具体物质2]纳米复合材料的抗菌潜力表明,其对XDR[细菌名称1]和VRSA菌株具有显著的抑制活性,抑菌圈直径可达50mm,MIC值分别为0.125至1μg/mL和1至8μg/mL。雄性Sprague Dawley大鼠体内试验结果显示,与阴性对照组相比,感染[细菌名称1]和[细菌名称2]后,生化、血液学和组织病理学检查结果出现显著变化。用负载有[具体物质1]或[具体物质2]的壳聚糖纳米颗粒治疗后,这些值恢复到正常范围。实时定量聚合酶链反应(RT - qPCR)结果表明,在整个实验期间,尤其是与阳性对照组相比,用负载有[具体物质1]或[具体物质2]的壳聚糖纳米颗粒治疗后,[基因名称1]基因的相对表达显著上调,[基因名称2]基因的表达下调。总之,这是第一份表明含壳聚糖纳米颗粒的[具体物质1]和[具体物质2]纳米复合材料有望成为对抗XDR[细菌名称1]和VRSA感染以及管理炎症情况和氧化应激相关疾病的有力竞争者的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e528/11047512/d98746a529a2/antioxidants-13-00428-g009.jpg
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