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KMID : 0370019960100000203
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Chung-Ang Journal of Pharmacal Sciences
1996 Volume.10 No. 0 p.203 ~ p.219
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Effect of BOSENTAN, EndoethelinAB receptor antagonist Experimental Allergic Encephalomyelitis
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Abstract
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Experimental allergic encephalomyelitis (EAE) is an animal model of autoimmune disease such as multiple sclerosis.
Endothelin-1, isolated from porcine aorta foremostly, is a potent vasoconstrictor peptide and acts as a mitogen and chemotaxtic factor.
In present study, the level of endothelin-1 (ET-1) in blood, brain and spinal cord of EAE-induced Lewis rat was evaluated through radioimmunoassay. In addition, for investigating the role of ET-1 on pathogenesis of EAE, intracisternal injection of mixed ET-1 receptor antagonist, BOSENTAN to Lewis rats which was at it´s preclinical, Grade 1, and Grade 3 stage was done.
At the severe stage of EAE (Grade 3), ET-1 level in the spinal cord of EAE induced rats increased two-folds (p<0.05) compared with that of sham-treated rats.
In bosentan (300nmol/day, i.c.) treatment study, bosentan effectively ameliorated the clinical severity of EAE at all stages of EAE.
These findings suggest that ET-1 plays an important role in the progression of clinical symptom of EAE. Amelioration of clinical symptom of EAE by bosentan implies a therapeutic possibility of ET-1 antagonist treatment in multiple sclerosis and it´s animal model. EAE.
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KEYWORD
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