Inhibitory effects of edaravone, a free radical scavenger, on cytokine-induced hyperpermeability of human pulmonary microvascular endothelial cells: A comparison with dexamethasone and nitric oxide synthase inhibitor

Yukie Saito, Yousuke Fujii, Masato Yashiro, Mitsuru Tsuge, Nobuyuki Nosaka, Nobuko Yamashita, Mutsuko Yamada, Hirokazu Tsukahara, Tsuneo Morishima

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Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the transhuman PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α + IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.

Original languageEnglish
Pages (from-to)279-290
Number of pages12
JournalActa medica Okayama
Issue number5
Publication statusPublished - Jan 1 2015



  • Edaravone
  • Permeability
  • Pulmonary microvascular endothelial cells
  • Vascular endothelial-cadherin
  • Zonula occludens-1 protein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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