Serofendic Acid Protects Against Myocardial Ischemia–Reperfusion Injury in Rats

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  • Ioroi Tadaaki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Akao Masaharu
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan Department of Cardiology, National Hospital Organization Kyoto Medical Center, Japan
  • Iguchi Moritake
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan Department of Cardiology, National Hospital Organization Kyoto Medical Center, Japan
  • Kato Masashi
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan
  • Kimura Takeshi
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan
  • Izumi Yasuhiko
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Akaike Akinori
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Graduate School of Pharmaceutical Sciences, Nagoya University, Japan
  • Kume Toshiaki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

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Abstract

We previously reported that serofendic acid, a lipophilic extract of fetal calf serum, protects against oxidative stress in primary culture of neonatal rat cardiomyocytes. However, the effect of serofendic acid on myocardial ischemia–reperfusion injury in vivo is yet to be determined. In the present study, we investigated the effect of intravenous administration of serofendic acid on ischemia–reperfusion injury induced by transient occlusion of the left coronary artery in rats. The rat heart was subjected to 25-min ischemia followed by 2-h reperfusion. Bolus intravenous administration of serofendic acid (1 – 10 mg/kg) given twice reduced the infarct volume in a dose-dependent manner. The protective effect of serofendic acid was abolished by pretreatment with 5-hydroxydecanoate, a blocker of mitochondrial ATP-sensitive potassium channels. For further testing of the protective effect of serofendic acid at the subcellular level, we monitored mitochondrial membrane potential (MMP) in individual cells using real-time two-photon imaging of Langendorff-perfused rat heart. A 25-min no-flow ischemia, followed by reperfusion caused progressive MMP loss. Serofendic acid significantly reduced the number of cells undergoing MMP loss. These results suggest that serofendic acid protected cardiac myocytes against myocardial ischemia–reperfusion injury by preserving the functional integrity of mitochondria.

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