Serofendic acid, a substance extracted from fetal calf serum, as a novel drug for cardioprotection.
We previously identified a novel endogenous substance, serofendic acid, from a lipophilic extract of fetal calf serum. The compound, a low-molecular-weight sulfur-containing atisane-type diterpenoid, exhibited potent protective action against neurotoxicity induced by glutamate, nitric oxide, and oxidant stress. We investigated whether this substance has a cardioprotective effect. Primary cultures of neonatal rat cardiac myocytes were exposed to oxidant stress (H2O2) to induce cell death. Pretreatment with serofendic acid significantly suppressed cell death induced by H2O2, and the cytoprotective effect was closely associated with the preservation of mitochondrial function. Serofendic acid inhibited H2O2-induced loss of mitochondrial membrane potential in a concentration-dependent manner (with saturation by 100 microM), by attenuating matrix calcium overload and intracellular accumulation of reactive oxygen species. The protective effect of serofendic acid was comparable to that of a mitochondrial ATP-sensitive potassium (mitoK ATP) channel opener, diazoxide. Furthermore, mitoK ATP channel blocker, 5-hydroxydecanoate, abolished the protective effect of serofendic acid. Serofendic acid and diazoxide, administered together, at 100 microM each, had no additive effects. Thus, serofendic acid inhibited the oxidant-induced mitochondrial death pathway, presumably through activation of the mitoK(ATP) channel. In conclusion, serofendic acid appears to protect cardiac myocytes from oxidant-induced cell death by preserving the functional integrity of mitochondria. Our findings suggest that serofendic acid may represent a novel candidate for cardioprotective therapy in ischemia/reperfusion injury.
Akao
Masaharu
M
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. akao@kuhp.kyoto-u.ac.jp
Takeda
Toshihiro
T
Kita
Toru
T
Kume
Toshiaki
T
Akaike
Akinori
A
D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D002417:Cattle; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D005312:Fetal Blood / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy
D002316:Cardiotonic Agents; D004224:Diterpenes; C452642:serofendic acid