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  2. Anti-EMT properties of ergothioneine attenuate lipopolysaccharide-induced oxidative stress-mediated acute lung injury via modulating TGF-β/smad/snail signaling pathway

Anti-EMT properties of ergothioneine attenuate lipopolysaccharide-induced oxidative stress-mediated acute lung injury via modulating TGF-β/smad/snail signaling pathway

  • Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231178015. doi: 10.1177/09603271231178015.
Shabnoor Iqbal 1 Farhat Jabeen 1 Noman Aslam 2 Maria Manan 3
Affiliations

Affiliations

  • 1 Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.
  • 2 College of Food Sciences & Technology, Huazhong Agriculture University, Wuhan China.
  • 3 Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan.
Abstract

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.

Keywords

NF-Kb; acute lung injury; e-cadherin; inflammation; oxidative stress; snail; vimentin.

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