Yakut Seda, Gelen Volkan, Kara Hülya, Özkanlar Seçkin, Yeşildağ Ali
Department of Histology and Embryology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
Department of Physiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey.
Environ Toxicol. 2024 Nov;39(11):4960-4973. doi: 10.1002/tox.24369. Epub 2024 Jul 9.
Toll-like receptor 4 (TLR-4) ligands were initially shown to be the source of lipopolysaccharide (LPS), a gram-negative bacterium's cell wall immunostimulatory component. Oxidative stress, apoptosis, and inflammation are all potential effects of LPS treatment on the lungs. By triggering oxidative stress and inflammation, these negative effects could be avoided. Robust flavonoid oleuropein (OLE) exhibits anti-inflammatory, antiproliferative, and antioxidative properties. A nanodelivery system could improve its low bioavailability, making it more effective and useful in treating chronic human ailments. This study evaluates the effects of AgNP-loaded OLE on LPS-induced lung injury in rats in terms of TLR4/P2X7 receptor-mediated inflammation and apoptosis. Forty-eight male albino rats were randomly divided into eight groups. Drugs were administered to the groups in the doses specified as follows: Control, LPS (8 mg/kg ip), OLE (50 mg/kg) AgNPs (100 mg/kg), OLE + AgNPs (50 mg/kg), LPS + OLE (oleuropein 50 mg/kg ig + LPS 8 mg/kg ip), LPS + AgNPs (AgNPs 100 mg/kg ig + LPS 8 mg/kg ip), and LPS + OLE + AgNPs (OLE + AgNPs 50 mg/kg + LPS 8 mg/kg ip). After the applications, the rats were decapitated under appropriate conditions, and lung tissues were obtained. Oxidative stress (SOD, MDA, and GSH), and inflammation (IL-6, IL-1β, TNF-α, Nrf2, P2X7R, AKT, and TLR4) parameters were evaluated in the obtained lung tissues. Additionally, histopathology studies were performed on lung tissue samples. The data obtained were evaluated by comparison between groups. Both OLE and OLE + AgNPs showed potential in reducing oxidative stress, inflammation, and apoptosis (p < 0.05). These findings were supported by histopathological analysis, which revealed that tissue damage was reduced in OLE and OLE + AgNPs-treated groups. According to the results, LPS-induced lung injury can be reduced by using nanotechnology and producing OLE + AgNP.
Toll样受体4（TLR-4）配体最初被证明是脂多糖（LPS）的来源，脂多糖是革兰氏阴性细菌细胞壁的免疫刺激成分。LPS处理对肺部的潜在影响包括氧化应激、细胞凋亡和炎症。通过引发氧化应激和炎症，可以避免这些负面影响。强大的类黄酮橄榄苦苷（OLE）具有抗炎、抗增殖和抗氧化特性。纳米递送系统可以提高其低生物利用度，使其在治疗人类慢性疾病方面更有效且更有用。本研究从TLR4/P2X7受体介导的炎症和细胞凋亡方面评估了负载银纳米颗粒的OLE对LPS诱导的大鼠肺损伤的影响。48只雄性白化大鼠被随机分为八组。按照以下指定剂量给各组给药：对照组、LPS（8mg/kg腹腔注射）、OLE（50mg/kg）、银纳米颗粒（100mg/kg）、OLE+银纳米颗粒（50mg/kg）、LPS+OLE（橄榄苦苷50mg/kg灌胃+LPS 8mg/kg腹腔注射）、LPS+银纳米颗粒（银纳米颗粒100mg/kg灌胃+LPS 8mg/kg腹腔注射）以及LPS+OLE+银纳米颗粒（OLE+银纳米颗粒50mg/kg+LPS 8mg/kg腹腔注射）。给药后，在适当条件下将大鼠断头，获取肺组织。对获取的肺组织评估氧化应激（超氧化物歧化酶、丙二醛和谷胱甘肽）和炎症（白细胞介素-6、白细胞介素-1β、肿瘤坏死因子-α、核因子E2相关因子2、P2X7受体、蛋白激酶B和TLR4）参数。此外，对肺组织样本进行了组织病理学研究。通过组间比较评估所获得的数据。OLE和OLE+银纳米颗粒在降低氧化应激、炎症和细胞凋亡方面均显示出潜力（p<0.05）。组织病理学分析支持了这些发现，该分析表明OLE和OLE+银纳米颗粒处理组的组织损伤有所减轻。根据结果，使用纳米技术制备OLE+银纳米颗粒可以减轻LPS诱导的肺损伤。
