Synergistic efficacy of concurrent treatment with cilostazol and probucol on the suppression of reactive oxygen species and inflammatory markers in cultured human coronary artery endothelial cells.
In the present study, we aimed to identify the synergistic effects of concurrent treatment of low concentrations of cilostazol and probucol to inhibit the oxidative stress with suppression of inflammatory markers in the cultured human coronary artery endothelial cells (HCAECs). Combination of cilostazol (0.3~3 microM) with probucol (0.03~0.3 microM) significantly suppressed TNF-alpha-stimulated NAD(P)H-dependent superoxide, lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production and TNF-alpha release in comparison with probucol or cilostazol alone. The combination of cilostazol (0.3~3 microM) with probucol (0.1~0.3 microM) inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) more significantly than did the monotherapy with either probucol or cilostazol. In line with these results, combination therapy significantly suppressed monocyte adhesion to endothelial cells. Taken together, it is suggested that the synergistic effectiveness of the combination therapy with cilostazol and probucol may provide a beneficial therapeutic window in preventing atherosclerosis and protecting from cerebral ischemic injury.
Park
So Youn
SY
Department of Pharmacology Pusan National University College of Medicine, Busan 602-739, Korea.
Lee
Jeong Hyun
JH
Shin
Hwa Kyoung
HK
Kim
Chi Dae
CD
Lee
Won Suk
WS
Rhim
Byung Yong
BY
Shin
Yung Woo
YW
Hong
Ki Whan
KW