MCI-186 (edaravone), a novel free radical scavenger, protects against acute autoimmune myocarditis in rats.
In this study, we tested the hypothesis that MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one; edaravone), a novel free radical scavenger, protects against acute experimental autoimmune myocarditis (EAM) in rats by the radical scavenging action associated with the suppression of cytotoxic myocardial injury. Recent evidence suggests that oxidative stress may play a role in myocarditis. We administered MCI-186 intraperitoneally at 1, 3, and 10 mg.kg(-1).day(-1) to rats with EAM for 3 wk. The results were compared with untreated rats with EAM. MCI-186 treatment did not affect hemodynamics. MCI-186 treatment (3 and 10 mg.kg(-1).day(-1)) reduced the severity of myocarditis as assessed by comparing the heart-to-body weight ratio and pathological scores. Myocardial interleukin-1beta (IL-1beta)-positive cells and myocardial oxidative stress overload with DNA damage in rats with EAM given MCI-186 treatment were significantly less compared with those of the untreated rats with EAM. In addition, MCI-186 treatment decreased not only the myocardial protein carbonyl contents but also the myocardial thiobarbituric acid reactive substance products in rats with EAM. The formation of hydroxyl radicals in MCI-186-treated heart homogenates was decreased compared with untreated heart homogenates. Furthermore, cytotoxic activities of lymphocytes of rats with EAM treated with MCI-186 were significantly lower compared with those of the untreated rats with EAM. Hydroxyl radicals may be involved in the development of myocarditis. MCI-186 protects against acute EAM in rats associated with scavenging hydroxyl free radicals, resulting in the suppression of autoimmune-mediated myocardial damage associated with reduced oxidative stress state.
Nimata
Masaomi
M
Dept. of Cardiovascular Medicine, Graduate School of Medicine, Kyoto Univ., 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Okabe
Taka-aki
TA
Hattori
Miki
M
Yuan
Zuyi
Z
Shioji
Keisuke
K
Kishimoto
Chiharu
C
D000208:Acute Disease; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D009205:Myocarditis / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D016207:Cytokines; D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine