title: Serofendic acid protects against myocardial ischemia-reperfusion injury in rats.
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.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Ioroi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Akao
authors.forename: Moritake
authors.initials: M
authors.lastname: Iguchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Izumi
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019610:Cytoprotection; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004224:Diterpenes; D015221:Potassium Channels; D020011:Protective Agents; C117780:mitochondrial K(ATP) channel; C452642:serofendic acid