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

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2025-05-05 DOI:10.1111/fcp.70014

Sahar Khateeb, Amal I. Hassan

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引用次数: 0

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.

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奈米结构的依托昔布脂质载体在大鼠中减轻辐射引起的肺部炎症和探索抗炎机制的研究

辐射暴露会引起炎症，而消炎药依托昔布（etoricoxib， ET）可能会减轻炎症。目的探讨依托瑞昔布纳米结构脂质载体（ET-NLCs）对大鼠放射性急性肺炎症的缓解作用。方法36只大鼠随机分为6组。第1组(C)：对照组；2组（ET）：正常大鼠口服ET (10 mg/kg) 14 d；3组（ET-NLC）：正常大鼠口服ET-NLC (10 mg/kg)，连续14天。第4组(R)：大鼠全身暴露于6 Gy γ射线，此后未经处理，诱导肺部炎症和损伤。第5组（ET- r），辐照大鼠，每日口服ET (10 mg/kg)，连续14 d。第6组（ET-NLC-R），辐照大鼠，每日口服et - nlc (10 mg/kg)，连续14 d。通过分子、生化和组织病理学分析来评估炎症、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表达减少81.5%，细胞凋亡增加。ET-NLCs治疗逆转了这些作用，Bax降低59.9%，Bcl-2增加337.4%。此外，与单独的辐射暴露相比，ET-NLCs使caspase-3和caspase-8的激活分别降低了54.5%和62.9%。此外，与辐照组相比，ET-NLCs通过降低白细胞介素-6 （IL-6）和肿瘤坏死因子-α (TNF-α)水平分别降低49%和39%，显示出强大的抗炎作用。辐射使丙二醛（MDA）水平升高388%，表明氧化损伤，并抑制过氧化氢酶（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处理使MDA水平降低35.7%，使CAT、GPX和SOD水平升高4766.7%和765.9%，恢复了抗氧化平衡。辐射使表面活性剂蛋白（SP-D）水平降低到控制值的4.9%，但ET-NLCs治疗使其恢复到14%。组织病理学分析显示，辐射暴露的肺显示肺泡间隔增厚，肺气肿区和炎症浸润。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。基于这些结果，NLCs是最有希望提供抗炎药物治疗辐射引起的肺损伤的方法之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.