The effect of cloricromene, a coumarine derivative, on leukocyte accumulation, myocardial necrosis and TNF-alpha production in myocardial ischaemia-reperfusion injury
Autor: | Mariapatrizia Ioculano, Domenica Altavilla, Alfredo Miceli, Giuseppe M. Campo, Gioacchino Calapai, Basilia Zingarelli, Archille P. Caputi, Francesco Squadrito, Marco Prosdocimi |
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Rok vydání: | 1993 |
Předmět: |
Male
medicine.medical_specialty Necrosis medicine.medical_treatment Ischemia Myocardial Reperfusion Injury General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Internal medicine medicine Leukocytes Animals General Pharmacology Toxicology and Pharmaceutics Creatine Kinase Peroxidase Analysis of Variance business.industry Tumor Necrosis Factor-alpha Cloricromene Chromonar General Medicine medicine.disease Survival Analysis Rats medicine.anatomical_structure Endocrinology Cytokine Circulatory system Immunology Tumor necrosis factor alpha medicine.symptom business Reperfusion injury Artery |
Zdroj: | Life sciences. 53(4) |
ISSN: | 0024-3205 |
Popis: | The effects of cloricromene, a coumarine derivative, were studied in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 68 +/- 4%; necrotic area/total area = 48 +/- 3%) high serum creatinphosphokinase activity (Sham MI/R = 29 +/- 8 U/ml; MI/R = 205 +/- 11 U/ml) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation), in the area-at-risk (6.3 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (6.5 +/- 0.5 U x 10(-3)/g tissue). Furthermore, serum TNF-alpha was undetectable during the occlusion period, but upon the release of the coronary artery significantly increased. At the end of reperfusion, macrophage TNF-alpha was also enhanced. The administration of cloricromene (2 mg/kg, 5 minutes after the onset of reperfusion) significantly reduced myocardial injury (necrotic area/area-at-risk 30 +/- 1.3%; necrotic area/total area = 25 +/- 1.5) blunted the increase in serum creatinphosphokinase activity (92 +/- 5 U/ml) and lowered myeloperoxidase activity in area-at-risk (2.5 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (2.2 +/- 0.3 U x 10(-3)/g tissue) and decreased the serum and macrophage levels of TNF-alpha. These data indicate that cloricromene exerts beneficial effects on myocardial ischaemia/reperfusion injury. Finally, since we measured increased serum levels of TNF-alpha that were blunted by the cloricromene treatment, our data are consistent with an involvement of TNF-alpha in the reperfusion injury induced by myocardial ischaemia. |
Databáze: | OpenAIRE |
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