Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.
College of Food Sciences & Technology, Huazhong Agriculture University, Wuhan China.
Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231178015. doi: 10.1177/09603271231178015.
Acute lung injury (ALI) is a heterogeneous pulmonary illness that is fast developing and has a high fatality rate. The current investigation set out to interpret the convergence of oxidative stress, inflammatory cytokines, TNF-α, snail, vimentin, e-cadherin, and NF-kB activation in ALI pathology. The outcome of assays of oxidative stress, ELISA, and western blot showed the declined of CAT, SOD, GPx, IL-1β, TNF-α, and upregulation of TGF-β, smad2/3, smad4, NF-kB, snail, and vimentin, concurrently with downregulation of e-cadherin expression in lung tissues as well as BALF in LPS-injected rats. The photomicrographs of the lungs marked severe congestion, infiltration of cytokines, and thickening of the alveolar walls. Pretreatments of ergothioneine after LPS-induced ALI, inhibited EMT-induction by blocking TGF-β, smad2/3, smad4, snail, vimentin, NF-kB, and inflammatory cytokines, and increased the expression of E-cadherin and antioxidant levels in a dose-dependent manner. These events helped to restore lung histoarchitecture and reduce acute lung injury. The present findings suggest that ergothioneine at 100 mg/kg is as effective as febuxostat (reference drug). The study concluded that ergothioneine may be replaced with febuxostat as a treatment option for ALI owing to its side effects after clinical trials for pharmaceutical purposes.
急性肺损伤（ALI）是一种异质性肺病，发展迅速，死亡率高。本研究旨在探讨氧化应激、炎症细胞因子、TNF-α、蜗牛、波形蛋白、E-钙粘蛋白和 NF-κB 激活在 ALI 发病机制中的汇聚。氧化应激、ELISA 和 Western blot 检测结果表明，LPS 注射大鼠肺组织和 BALF 中 CAT、SOD、GPx、IL-1β、TNF-α 下降，TGF-β、smad2/3、smad4、NF-κB、蜗牛和波形蛋白上调，E-钙粘蛋白表达下调。肺组织的照片显示严重充血、细胞因子浸润和肺泡壁增厚。LPS 诱导的 ALI 后用麦硫因预处理，通过阻断 TGF-β、smad2/3、smad4、蜗牛、波形蛋白、NF-κB 和炎症细胞因子来抑制 EMT 诱导，并呈剂量依赖性增加 E-钙粘蛋白的表达和抗氧化水平。这些事件有助于恢复肺组织形态结构并减轻急性肺损伤。本研究结果表明，麦硫因在 100mg/kg 时与非布司他（对照药物）一样有效。该研究得出结论，由于麦硫因在临床试验中的副作用，它可能会取代非布司他作为 ALI 的治疗选择。
