[Protective effect of mitochondrial antioxidant SkQl at cardiac ischemia and reperfusion].
Mitochondria are believed to be both main origin and target of oxidative stress in cells. In the present study we used novel mitochondria-targeted antioxidant SkQ1 using triphenylphosphonium cation as a driver. The substance was alimentary given to rats daily during 3 weeks in varying doses, from 0.5 to 250 mol/kg/day. The isolated hearts were perfused by standard procedure, the isovolumic left ventricular pressure was recorded. After stabilization period the hearts were subjected to 30-min total normothermic ischemia with subsequent 50-min reperfusion. Arrhythmic disorders at the onset of reperfusion were significantly less pronounced in SkQ1 groups 0.5 and 5 mol/kg, the arrhythmia index for first 30-min was 1.3+/-0.3 and 1.8+/-0.6, respectively, vs. 5.7+/-1.3 in control experiments. By the end of reperfusion a significantly better recovery of heart rate was observed in SkQ1 groups 0.5 and 250 mol/kg and that of developed pressure - in SkQ1 group 0.5 mol/kg. As a result, a recovery of the double product of developed pressure and heart rate by the end of reperfusion was almost twice higher in groups SkQ1 0.5 and 250 mol/kg (55+/-5 and 58+/-8%, respectively), vs. the control (30+/-4%, p<0.05). Results suggest that the protective action of SkQ1 at postischemic reperfusion may be due to increased myocardial antioxidant status.
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Lakomkin
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Kapel'ko
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010971:Plastoquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome; D017725:Ventricular Pressure / Q000187:drug effects
C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D017382:Reactive Oxygen Species; D010971:Plastoquinone