依托考昔纳米结构脂质载体减轻大鼠辐射诱导的肺部炎症及抗炎机制探究

Insights into nanostructured lipid carriers of etoricoxib for mitigating radiation-induced lung inflammation and exploring anti-inflammatory mechanisms in rats.

作者信息

Khateeb Sahar, Hassan Amal I

机构信息

Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, 71491, Saudi Arabia.

Biochemistry Division, Department of Chemistry, Faculty of Science, Fayoum University, Fayoum, Egypt.

出版信息

Fundam Clin Pharmacol. 2025 Jun;39(3):e70014. doi: 10.1111/fcp.70014.

DOI:10.1111/fcp.70014

PMID:40325971

Abstract

BACKGROUND

Radiation exposure can cause inflammation, which etoricoxib (ET), an anti-inflammatory drug, could potentially mitigate.

OBJECTIVE

This study aimed to evaluate the potential effectiveness of etoricoxib-loaded nanostructured lipid carriers (ET-NLCs) in mitigating radiation-induced acute lung inflammation in rats.

METHODS

Thirty-six rats were divided into six groups. Group 1 (C): control; group 2 (ET): normal rats given ET (10 mg/kg) orally for 14 days; group 3 (ET-NLC): normal rats administered ET-NLCs orally (10 mg/kg) for 14 days. Group 4 (R): rats exposed to 6 Gy whole-body gamma radiation, untreated thereafter to induce lung inflammation and injury. Group 5 (ET-R), irradiated rats, were administered ET (10 mg/kg) orally daily for 14 days. Group 6 (ET-NLC-R), irradiated rats, were administered ET-NLCs (10 mg/kg) orally daily for 14 days. Molecular, biochemical, and histopathological analyses were performed to assess inflammation, apoptosis, oxidative stress, and lung tissue architecture.

RESULTS

Radiation exposure led to a 1053% increase in Bax expression and an 81.5% decrease in Bcl-2, indicating heightened apoptosis. ET-NLCs treatment reversed these effects, reducing Bax by 59.9% and increasing Bcl-2 by 337.4%. Additionally, ET-NLCs reduced caspase-3 and caspase-8 activation by 54.5% and 62.9%, respectively, compared to radiation exposure alone. Furthermore, ET-NLCs demonstrated potent anti-inflammatory effects by reducing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels by 49% and 39%, respectively, compared to the irradiated group. Radiation increased malondialdehyde (MDA) levels by 388%, indicating oxidative damage, and suppressed antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). ET-NLC treatment decreased MDA levels and increased CAT, GPX, and SOD by 35.7%, 4766.7%, and 765.9%, respectively, restoring antioxidant balance. Radiation reduced surfactant protein (SP-D) levels to 4.9% of control values, but ET-NLCs treatment restored them to 14%. Histopathological analysis revealed that radiation-exposed lungs showed thickened inter-alveolar septa, emphysematous areas, and inflammatory infiltration. ET-NLCs treatment exhibited only mild thickening and limited inflammatory cell infiltration, suggesting significant improvement in lung architecture.

CONCLUSIONS

Based on these results, NLCs are one of the most promising ways to deliver anti-inflammatory drugs for treating lung damage caused by radiation.

摘要

背景

辐射暴露可引发炎症，而抗炎药物依托考昔（ET）可能具有减轻炎症的作用。

目的

本研究旨在评估载有依托考昔的纳米结构脂质载体（ET-NLCs）减轻大鼠辐射诱导的急性肺部炎症的潜在效果。

方法

将36只大鼠分为6组。第1组（C）：对照组；第2组（ET）：正常大鼠口服ET（10mg/kg），持续14天；第3组（ET-NLC）：正常大鼠口服ET-NLCs（10mg/kg），持续14天。第4组（R）：接受6Gy全身γ射线辐射的大鼠，此后未接受治疗以诱导肺部炎症和损伤。第5组（ET-R），辐射大鼠，每天口服ET（10mg/kg），持续14天。第6组（ET-NLC-R），辐射大鼠，每天口服ET-NLCs（10mg/kg），持续14天。进行分子、生化和组织病理学分析以评估炎症、细胞凋亡、氧化应激和肺组织结构。

结果

辐射暴露导致Bax表达增加1053%，Bcl-2减少81.5%，表明细胞凋亡加剧。ET-NLCs治疗逆转了这些效应，使Bax减少59.9%，Bcl-2增加337.4%。此外，与单独辐射暴露相比，ET-NLCs分别使caspase-3和caspase-8的激活减少54.5%和62.9%。此外，与辐射组相比，ET-NLCs通过分别降低白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平49%和39%，显示出强大的抗炎作用。辐射使丙二醛（MDA）水平增加388%，表明存在氧化损伤，并抑制了过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPX）和超氧化物歧化酶（SOD）等抗氧化酶。ET-NLC治疗降低了MDA水平，并分别使CAT、GPX和SOD增加35.7%、4766.7%和765.9%，恢复了抗氧化平衡。辐射使表面活性蛋白（SP-D）水平降至对照值的4.9%，但ET-NLCs治疗将其恢复至14%。组织病理学分析显示，辐射暴露的肺部表现为肺泡间隔增厚、肺气肿区域和炎症浸润。ET-NLCs治疗仅表现出轻度增厚和有限的炎症细胞浸润，表明肺结构有显著改善。