Generic placeholder image

Current Neurovascular Research


ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

The Phosphodiesterase III Inhibitor Cilostazol Ameliorates Ethanolinduced Endothelial Dysfunction

Author(s): Toshinori Takagi, Keisuke Mishiro, Masamitsu Shimazawa, Shinichi Yoshimura, Toru Iwama and Hideaki Hara

Volume 11, Issue 4, 2014

Page: [302 - 311] Pages: 10

DOI: 10.2174/1567202611666140912113152

Price: $65


Intracranial hemorrhage (ICH) remains a devastating disease, and heavy alcohol consumption is an underlying risk factor. The aim of this study was to study the mechanism of ethanol-induced endothelial cell damage and to evaluate the protective effect of cilostazol against ethanol-induced damage. We first evaluated transendothelial electrical resistance (TEER) and cell viability of human brain microvascular endothelial cells at the ethanol concentration shown to cause mild-to-moderate intoxication in the clinic. We also assessed the permeability of fluorescein isothiocyanate (FITC)- dextran and the change in tight junction proteins. Furthermore, we studied the potential of cilostazol to protect endothelial cells from ethanol-induced dysfunction. Concentration- and time-dependent effects of ethanol on cell viability and TEER showed that TEER was reduced at each concentration of ethanol tested during exposures of >2 h, but cell viability was not changed. Permeability of FITC-dextran was enhanced, and both tight junction and adherens junction proteins were reduced by 3-h ethanol treatment. The permeability of FITC-dextran was ameliorated by administration of cilostazol in a concentration-dependent manner. The protective effect of cilostazol was obstructed by administration of a protein kinase A inhibitor. Using gelatin zymography, we found that the protective effect of cilostazol was by reducing matrix metalloproteinase 9 (MMP-9) activation, but it had no effect on reactive oxygen spices (ROS). Our results indicate that cilostazol protected endothelial cells against ethanol-induced endothelial dysfunction by inhibiting ROS-mediated activation of MMP-9.

Keywords: Cilostazol, endothelial cell, ethanol, matrix metalloproteinase, phosphodiesterase III inhibitor, reactive oxygen species, tight junction.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy