EUK-8 a synthetic catalytic scavenger of reactive oxygen species protects isolated iron-overloaded rat heart from functional and structural damage induced by ischemia/reperfusion.
The effects of EUK-8, a synthetic, catalytic scavenger of reactive oxygen species, on isolated iron-overloaded rat hearts submitted to ischemia-reperfusion were studied. In the absence of EUK-8, functional parameters (systolic and diastolic pressures, oxygen consumption as estimated by the product heart rate times left ventricular diastolic pressure) were severely impaired 1 minute and 15 minutes after reperfusion following a 15 minute ischemic episode. Dimethylthiourea (10 mM), a hydroxyl radical scavenger, had a minimally protective effect. In contrast, EUK-8 at a concentration of 50 microM in the perfusion medium maintained these parameters at close to their preischemia values. Electron microscopic analysis of heart tissues after 15 minutes ischemia followed by 15 minutes reperfusion showed extensive damage to mitochondria and sarcomeres in untreated hearts, while the extent of damage was significantly lower in EUK-8-treated hearts. The functional and structural protection afforded by EUK-8 were significantly better than those induced by dimethylthiourea. These data suggest that EUK-8 may be therapeutically useful in preventing heart damage induced by ischemia-reperfusion, for example, during thrombolytic treatment of myocardial infarction.
Pucheu
S
S
Groupe de Physiopathologie Cellulaire Cardiaque, URA CNRS, Université Joseph Fourier, Grenoble, France.
Boucher
F
F
Sulpice
T
T
Tresallet
N
N
Bonhomme
Y
Y
Malfroy
B
B
de Leiris
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003911:Dextrans / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D005029:Ethylenediamines / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000648:ultrastructure; D007501:Iron / Q000008:administration & dosage / Q000633:toxicity; D008345:Manganese / Q000378:metabolism; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D003911:Dextrans; D005029:Ethylenediamines; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D008345:Manganese; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); C038983:1,3-dimethylthiourea; D007501:Iron; D013890:Thiourea