Background: Recently, it has become apparent that
reactive oxygen species (ROS) play a critical role in the initiation of
atherosclerosis. In this study, the effect of radical scavenger edaravone to
the leukocyte rolling and to the expression of adhesion molecules on microvascular
endothelium was investigated. Methods: DSS
induced rat colitis model was used as an inflammation model. Edaravone (10.5 mg/kg,
Mitsubishi Tanabe Pharma Corporation, Japan) was used to examine the action
of ROS. Images of leukocyte rolling in mesenteric microvessels were investigated
in a fluorescence bio-imaging model. Each cross section from the target blood
vessel (aotic root, aorta, superior mesenteric artery) were examined by immune-peroxidase
staining with anti-P-selectin, E-selectin,
ICAM-1 antibody using the streptavidin/biotinylated
horseradish peroxidase method. Results: 1) Leukocyte rolling in mesenteric
microvessels was significantly increased in colitis. The number of rolling
leukocyte was significantly decreased in edaravone group than placebo group
(501.3 ± 39.2 vs 252.2 ± 37.2 count/100 μm/10 min). 2) The expression of
P-selectin in endothelial cell was significantly increased in colitis. However,
this expression was decreased in edaravone group. 3) The expression of
E-selectin was not induced to intact aortic root and aorta. In the superior
mesenteric artery, the expression was induced by inflammation, and it was
attenuated by edaravone. 4) There was little expression of ICAM-1 in both
intact aortic root and aortas. While, in the superior mesenteric artery, the
expression was confirmed only in placebo group in colitis, and it was
attenuated in edaravone group. Conclusions: It was suggested that administration
of edaravone led to improving a haemostasis of microcirculation based on
down-regulation of adhesion molecules. These results support the evidence that
ROS plays a critical role in micro- vascular dysfunction.
Cite this paper
Sakamoto, K. , Yamashita, T. , Yamanishi, H. and Yamamoto, J. (2013) The effect of edaravone to leukocyte rolling and adhesion molecule expression in microvessels. Health, 5, 402-408. doi: 10.4236/health.2013.53054.
 Jambunathan, N. (2010) Determination and detection of reactive oxygen species (ROS), lipid peroxidation, and electrolyte leakage in plants. Methods in Molecular Biology, 639, 292-298. doi:10.1007/978-1-60761-702-0_18
 Yamashita, T., Oda, E., Sano, T., Ijiru, Y., Giddings, J.C. and Yamamoto, J. (2005) Varying the ratio of dietary n-6/ n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/ LDLR-/ double knockout mouse. Thrombosis Re-search, 116, 393 401. doi:10.1016/j.thromres.2005.01.011
 Lu, M. and Gong, X. (2009) Upstream reactive oxidative species (ROS) signals in exogenous oxidative stress-induced mitochondrial dysfunction. Cell Biology International, 33, 658-664.
 Lau, A.T., Wang, Y. and Chiu, J.F. (2008) Reactive oxy gen species: Current knowledge and applications in cancer research and therapeutic. Journal of Cellular Biochemistry, 104, 657-667.
 Ozono, R., Brydun, A., Watari, Y., Yamamoto, Y. and Ohshima, T. (2007) Assessment of oxidative stress in patients with atherosclerosis focusing on heme oxygenase. Rinsho Byori, 55, 758-763.
 Barry-Lane, P.A., Patterson, C., van der Merwe, M., Hu, Z., Holland, S.M., Yeh, E.T. and Runge, M.S. (2001) p47 phox is required for atherosclerotic lesion progression in ApoE(-/-) mice. Journal of Clinical Investigation, 108, 1513-1522.
 Griendling, K.K., Sorescu, D., Lassegue, B. and Ushio Fukai, M. (2000) Modulation of protein kinase ac-tivity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterio scle-rosis, Thrombosis, and Vascular Biology, 20, 2175 2183.
 Ehara, S., Ueda, M., Naruko, T., Haze, K., Itoh, A., Otsuka, M., Komatsu, R., Matsuo, T., Itabe, H., Takano, T., Tsukamoto, Y., Yoshiyama, M., Takeuchi, K., Yoshi kawa, J. and Becker, A.E. (2001) Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation, 103, 1955-1960.
 Meisinger, C., Baumert, J., Khuseyinova, N., Loewel, H. and Koenig, W. (2005) Plasma oxidized low-density lipo protein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation, 112, 651-657.
 Eriksson, E.E. (2003) Leukocyte recruitment to atherosclerotic lesions, a complex web of dynamic cellular and molecular interactions. Current Drug Targets—Cardiovascular & Haematological Disorders, 3, 309-325.
 Eriksson, E.E. (2004) Mechanisms of leukocyte recruit ment to atherosclerotic lesions: Future prospects. Current Opinion in Lipidology, 15, 553-558.
 Tanaka, M. (2002) Pharmacological and clinical profile of the free radical scavenger edaravone as a neuropro-tective agent. Nihon Yakurigaku Zasshi, 119, 301-308.
 Xi, H., Akishita, M., Nagai, K., Yu, W., Hasegawa, H., Eto, M., Kozaki, K. and Toba, K. (2007) Potent free radical scavenger, edaravone, suppresses oxidative stress-induced endothelial damage and early atherosclerosis. Athe rosclerosis, 191, 281-289.
 Group, E.A.I.S. (2003) Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarc-tion. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovascular Diseases, 15, 222-229.
 Watanabe, T., Tahara, M. and Todo, S. (2008) The novel antioxidant edaravone: From bench to bedside. Cardio vascular Therapeutics, 26, 101-114.
 Yoshida, H., Yanai, H., Namiki, Y., Fukat-su-Sasaki, K., Furutani, N. and Tada, N. (2006) Neuroprotective effects of edaravone: A novel free radical scavenger in cerebro vascular injury. CNS Drug Reviews, 12, 9-20.
 Zhang, N., Komine-Kobayashi, M., Tanaka, R., Liu, M., Mizuno, Y. and Urabe, T. (2005) Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke, 36, 2220-2225.
 Watanabe, T., Yuki, S., Egawa, M. and Nishi, H. (1994) Protective effects of MCI-186 on cerebral ischemia: Possible involvement of free radical scavenging and antioxidant actions. Journal of Pharmacology and Experimental Therapeutics, 268, 1597-1604.
 Yoneda, Y., Uehara, T., Yamasaki, H., Kita, Y., Tabuchi, M. and Mori, E. (2003) Hos-pital-based study of the care and cost of acute ischemic stroke in Japan. Stroke, 34, 718-724.
 Barros, K.V., Xavier, R.A., Abreu, G.G., Martinez, C.A., Ribeiro, M.L., Gambero, A., Car-valho, P.O., Nascimento, C.M. and Silveira, V.L. (2010) Soy-bean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis. Lipids in Health and Disease, 9, 68. doi:10.1186/1476-511X-9-68
 Cooper, H.S., Murthy, S.N., Shah, R.S. and Sedergran, D.J. (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Laboratory Investi gation, 69, 238-249.
 Okayasu, I., Ha-takeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y. and Nakaya, R. (1990) A novel method in the induction of reliable experi-mental acute and chronic ulcerative colitis in mice. Gastroen-terology, 98, 694-702.
 Seki, J. (1990) Fiber-optic la-ser-Doppler anemometer mi croscope developed for the mea-surement of microvascular red cell velocity. Microvascular Re-search, 40, 302-316.
 Teraki, Y., Moriya, N. and Shiohara, T. (1994) Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption. American Journal of Pathology, 145, 550-560.
 Harrison, D., Griendling, K.K., Landmesser, U., Hornig, B. and Drexler, H. (2003) Role of oxidative stress in athe rosclerosis. American Journal of Cardiology, 91, 7A-11A.
 Foncea, R., Carvajal, C., Almarza, C. and Leighton, F. (2000) Endothelial cell oxida-tive stress and signal transduction. Biological Research, 33, 89-96.
 Takano, M., Meneshian, A., Sheikh, E., Yamakawa, Y., Wilkins, K.B., Hopkins, E.A. and Bulkley, G.B. (2002) Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation. American Journal of Physiology—Heart and Cir-culatory Physiology, 283, H2054-H2061.
 Rubio-Gayosso, I., Platts, S.H. and Duling, B.R. (2006) Reactive oxygen species mediate modification of glycol calyx during ischemia-reperfusion injury. American Jour nal of Physiology—Heart and Circulatory Physiology, 290, H2247-H2256.
 Ridker, P.M., Buring, J.E. and Rifai, N. (2001) Soluble P selectin and the risk of future cardiovascular events. Cir culation, 103, 491-495.
 Wan, M.X., Riaz, A.A., Schramm, R., Wang, Y., Vestwe ber, D., Menger, M.D. and Thorlacius, H. (2002) Leuko cyte rolling is exclusively mediated by P-selectin in colonic venules. British Journal of Pharmacology, 135, 1749 1756.
 Ley, K. and Tedder, T.F. (1995) Leukocyte interactions with vascular endothelium. New insights into selectin mediated attachment and rolling. The Journal of Immunology, 155, 525-528.
 Vainer, B., Horn, T. and Nielsen, O.H. (2006) Colonic epithelial cell expression of ICAM-1 relates to loss of surface continuity: A comparative study of inflammatory bowel disease and colonic neoplasms. Scandinavian Journal of Gastroenterology, 41, 318-325.
 Czech, W., Krutmann, J., Budnik, A., Schopf, E. and Kapp, A. (1993) Induction of intercellular adhesion molecule 1 (ICAM-1) expression in normal human eosinophils by inflammatory cytokines. Journal of Investigative Dermatology, 100, 417-423.
 Burke-Gaffney, A. and Hellewell, P.G. (1996) Tumour necrosis factor-alpha-induced ICAM-1 expres-sion in hu man vascular endothelial and lung epithelial cells: Modulation by tyrosine kinase inhibitors. British Journal of Phar macology, 119, 1149-1158.
 Hubbard, A.K. and Giardina, C. (2000) Regulation of ICAM-1 expression in mouse macrophages. Inflammation, 24, 115-125.