Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Folia Morphol (Warsz). 2021;80(2):392-402. doi: 10.5603/FM.a2020.0075. Epub 2020 Jul 9.
The intention of the present study was to assess the structural affection of the lung following methotrexate (MTX) overdose. The proposed underlying mechanisms involved in lung affection were studied. The possible modulation role of febuxostat over such affection was studied.
Twenty-four rats were divided into three groups: control, MTX-treated, febuxostat-treated. The study was continued for 2 weeks. Lung was processed for histological and immunohistochemical (inducible nitric oxide synthase [iNOS] and cyclooxygenase [COX]-2) studies. Inflammatory markers (tumour necrosis factor alpha [TNF-a], interleukin 1 [IL-1]), Western blot evaluation of nuclear factor kappa B (NF-kB) and oxidative/antioxidative markers were done.
Methotrexate-treated group exhibited inflammatory cellular infiltrations, thickened interalveolar septa, dilated congested blood vessels, extravasated blood, and apoptosis. The collagen fibres content increased 3-fold. MTX induced lung affection through oxidative stress (increase MDA/decrease GSH, SOD) and apoptosis. It induced sterile inflammation through an increase of NF-kB (2-fold), IL-1 (3-fold) and TNF-a (3-fold), COX-2 cells (2.5-fold) and iNOS (6-fold). With the use of febuxostat, the normal lung architecture was observed with a bit thickened interalveolar septum and extravasated blood. The collagen fibres content was minimal. Decrement of oxidative stress and sterile inflammation (COX-2 cells and iNOS were comparable to the control group. NF-kB, IL-1 and TNF-a became higher by 34%, 64% and 100%).
The overdose of MTX displays inflammatory lung affection with residual fibrosis. It induces lung affection through oxidative stress, apoptosis and sterile inflammation. With the use of febuxostat, the normal lung architecture was preserved with a little structural affection or fibrotic residue. Febuxostat exerts its lung protection through its anti-inflammatory and antioxidant features.
本研究旨在评估甲氨蝶呤（MTX）过量后肺的结构损伤。研究了涉及肺损伤的潜在机制，并研究了别嘌醇对这种损伤的可能调节作用。
将 24 只大鼠分为三组：对照组、MTX 处理组、别嘌醇处理组。研究持续 2 周。对肺进行组织学和免疫组织化学（诱导型一氧化氮合酶[iNOS]和环氧化酶[COX]-2）研究。检测炎症标志物（肿瘤坏死因子-α[TNF-α]、白细胞介素 1 [IL-1]）、核因子 kappa B（NF-kB）和氧化/抗氧化标志物的 Western blot 评估。
MTX 处理组表现出炎症细胞浸润、肺泡间隔增厚、扩张充血的血管、漏出的血液和细胞凋亡。胶原纤维含量增加了 3 倍。MTX 通过氧化应激（增加 MDA/减少 GSH、SOD）和细胞凋亡引起肺损伤。它通过增加 NF-kB（2 倍）、IL-1（3 倍）和 TNF-α（3 倍）、COX-2 细胞（2.5 倍）和 iNOS（6 倍）引起无菌性炎症。使用别嘌醇后，观察到正常的肺结构，肺泡间隔稍增厚，有漏出的血液。胶原纤维含量最小。氧化应激和无菌性炎症减少（COX-2 细胞和 iNOS 与对照组相当。NF-kB、IL-1 和 TNF-α分别增加了 34%、64%和 100%）。
MTX 过量会引起炎症性肺损伤和残余纤维化。它通过氧化应激、细胞凋亡和无菌性炎症引起肺损伤。使用别嘌醇后，肺结构保持正常，仅有轻微的结构损伤或纤维残留。别嘌醇通过其抗炎和抗氧化特性发挥其肺保护作用。
