Edaravone protects against methylglyoxal-induced barrier damage in human brain endothelial cells

Andrea E. Tóth, Fruzsina R. Walter, Alexandra Bocsik, Petra Sántha, Szilvia Veszelka, Lajos Nagy, László G. Puskás, Pierre Olivier Couraud, Fuyuko Takata, Shinya Dohgu, Yasufumi Kataoka, Mária A. Deli

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology: Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings: Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 μM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion: These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases.

Original languageEnglish
Article numbere100152
JournalPloS one
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 17 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Tóth, A. E., Walter, F. R., Bocsik, A., Sántha, P., Veszelka, S., Nagy, L., Puskás, L. G., Couraud, P. O., Takata, F., Dohgu, S., Kataoka, Y., & Deli, M. A. (2014). Edaravone protects against methylglyoxal-induced barrier damage in human brain endothelial cells. PloS one, 9(7), [e100152]. https://doi.org/10.1371/journal.pone.0100152