通过调节TLR4/P2X7受体介导的炎症和细胞凋亡缓解大鼠LPS诱导的急性肺损伤

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-07-09 DOI:10.1002/tox.24369
Seda Yakut, Volkan Gelen, Hülya Kara, Seçkin Özkanlar, Ali Yeşildağ
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引用次数: 0

摘要

Toll 样受体 4(TLR-4)配体最初被证明是一种革兰氏阴性细菌细胞壁免疫刺激成分脂多糖(LPS)的来源。氧化应激、细胞凋亡和炎症都是 LPS 治疗对肺部的潜在影响。通过引发氧化应激和炎症,可以避免这些负面影响。强效类黄酮油菜素(OLE)具有抗炎、抗增殖和抗氧化特性。纳米给药系统可以改善其生物利用率低的问题,使其在治疗人类慢性疾病方面更加有效和有用。本研究从 TLR4/P2X7 受体介导的炎症和细胞凋亡方面评估了 AgNP 负载的 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 8 组。各组的给药剂量如下:对照组、LPS(8 毫克/千克 ip)、OLE(50 毫克/千克)、AgNPs(100 毫克/千克)、OLE + AgNPs(50 毫克/千克)、LPS + OLE(油菜素 50 毫克/千克 ig + LPS 8 毫克/千克 ip)、LPS + AgNPs(AgNPs 100 毫克/千克 ig + LPS 8 毫克/千克 ip)和 LPS + OLE + AgNPs(OLE + AgNPs 50 毫克/千克 + LPS 8 毫克/千克 ip)。施药后,在适当条件下将大鼠断头,获取肺组织。在获得的肺组织中评估氧化应激(SOD、MDA 和 GSH)和炎症(IL-6、IL-1β、TNF-α、Nrf2、P2X7R、AKT 和 TLR4)参数。此外,还对肺组织样本进行了组织病理学研究。获得的数据通过组间比较进行评估。OLE 和 OLE + AgNPs 在减少氧化应激、炎症和细胞凋亡方面都显示出了潜力(p
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Silver Nanoparticles Loaded With Oleuropein Alleviates LPS-Induced Acute Lung Injury by Modulating the TLR4/P2X7 Receptor-Mediated Inflammation and Apoptosis in Rats

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.

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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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