Use of zafirlucast, cysteine-containing leukotriene antagonist, in epinephrine-induced heart injury.
Combination of preventive and repeated (after 12 h) injections of zafirlucast in a daily dose of 40 mg/kg to animals with epinephrine-induced heart injury essentially decreased the content of leukotriene C(4), but did not prevent the increase of leukotriene B(4)content in the blood, though decreased its content in comparison with the level observed 24 h after epinephrine injection by 11%. Two injections of zafirlucast had a favorable impact on serotonin content in the myocardium (this parameter decreased by 19%), promoted a decrease in epinephrine content and normalization of the norepinephrine/epinephrine ratio, did not change prostaglandin content and ratio, and slightly decreased histamine content in the myocardium. The effect of zafirlucast can be explained by a decrease of oxidative stress. Zafirlucast decreased blood content of myofibrillar fraction of creatine phosphokinase (by 22%) and slightly improved elastic characteristics of erythrocytes. These results suggest that zafirlucast can be added to combined therapy of necrotic, stress-induced, hypoxic, and ischemic injuries of the myocardium.
Gongadze
N V
NV
Department of Pharmacology, Tbilisi State Medical University.
Kezeli
T D
TD
D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004837:Epinephrine / Q000633:toxicity; D006335:Heart Injuries / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles; D007527:Isoenzymes / Q000097:blood; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000097:blood; D017997:Leukotriene C4 / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D048448:Phenylcarbamates; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
D007211:Indoles; D007527:Isoenzymes; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; D007975:Leukotriene B4; D017997:Leukotriene C4; D012701:Serotonin; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; C062735:zafirlukast; D004837:Epinephrine