Sildenafil Blunts Lung Inflammation and Oxidative Stress in a Rat Model of Cholestasis

Q4 Pharmacology, Toxicology and Pharmaceutics
M. Ommati, N. Abdoli, Meisam Firoozi, Alireza Akhlagh, Sahra Mazloomi, K. Mousavi, H. Niknahad, R. Heidari
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引用次数: 3

Abstract

Background: Cholestasis is a multifaceted disease that influences not only the function of the liver but also affects many other organs. In this context, cholestasis-induced lung injury is a significant clinical complication. Unfortunately, there is no precise therapeutic option against cholestasis-associated lung injury. It has been revealed that oxidative stress and inflammatory response play a role in cholestasis-induced pulmonary damage. Sildenafil is a phosphodiesterase enzyme inhibitor used in the management of erectile dysfunction. Meanwhile, several experiments revealed the effects of sildenafil on oxidative stress and inflammation. This study aimed to evaluate the effect of sildenafil on cholestasis-induced oxidative stress and inflammation in cholestasis-induced lung injury. Methods: Rats underwent bile duct ligation (BDL) to induce cholestasis. Bronchoalveolar lavage fluid (BALF) levels of inflammatory cells, cytokine, and immunoglobulin were monitored at (3, 7, and 14 days after BDL surgery). Moreover, lung tissue histopathological alterations and biomarkers of oxidative stress were evaluated. Results: A significant increase in BALF inflammatory cells, TNF-α, and immunoglobulin G (IgG) was evident in BDL animals. Moreover, the infiltration of inflammatory cells, vascular congestion, and hemorrhage were detected in the lung of BDL rats. Increased markers of oxidative stress were also evident in the lung of BDL animals. Sildenafil (10 and 20 mg/kg) significantly blunted inflammatory response, oxidative stress, and histopathological alterations in the lung of cholestatic animals. Conclusion: The effects of sildenafil on inflammatory response and oxidative stress biomarkers seems to play a crucial role in its protective properties in the lung of cholestatic animals.
西地那非减轻大鼠胆汁淤积模型的肺部炎症和氧化应激
背景:胆汁淤积症是一种多方面的疾病,不仅影响肝脏功能,而且影响许多其他器官。在这种情况下,胆汁淤积引起的肺损伤是一个重要的临床并发症。不幸的是,目前还没有针对胆汁淤积相关肺损伤的精确治疗方案。研究表明,氧化应激和炎症反应在胆汁淤积引起的肺损伤中起作用。西地那非是一种磷酸二酯酶抑制剂,用于治疗勃起功能障碍。同时,几项实验揭示了西地那非对氧化应激和炎症的影响。本研究旨在评价西地那非对胆汁淤积性肺损伤中氧化应激和炎症的影响。方法:采用胆管结扎法诱导大鼠胆汁淤积。在BDL手术后3、7和14天监测支气管肺泡灌洗液(BALF)中炎症细胞、细胞因子和免疫球蛋白的水平。此外,肺组织病理改变和氧化应激的生物标志物进行了评估。结果:BDL动物的BALF炎症细胞、TNF-α和免疫球蛋白G (IgG)明显升高。BDL大鼠肺内可见炎性细胞浸润、血管充血、出血。氧化应激标志物的增加在BDL动物的肺部也很明显。西地那非(10和20 mg/kg)显著减弱了胆汁淤积动物肺部的炎症反应、氧化应激和组织病理学改变。结论:西地那非对炎症反应和氧化应激生物标志物的影响似乎在其对胆汁淤积动物肺的保护作用中起关键作用。
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
CiteScore
0.10
自引率
0.00%
发文量
17
审稿时长
10 weeks
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