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.

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.

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / drug therapy
  • Acute Lung Injury* / metabolism
  • Animals
  • Cadherins / metabolism
  • Cytokines / metabolism
  • Ergothioneine* / pharmacology
  • Febuxostat / pharmacology
  • Lipopolysaccharides / toxicity
  • Lung / pathology
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Rats
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vimentin / metabolism

Substances

  • Cadherins
  • Cytokines
  • Ergothioneine
  • Febuxostat
  • Lipopolysaccharides
  • NF-kappa B
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Vimentin