OBJECTIVES: We examined whether serofendic acid (SFA) has protective effects against oxidative stress in cardiac myocytes. BACKGROUND: We previously identified a novel endogenous substance, SFA, from a lipophilic extract of fetal calf serum. Serofendic acid protects cultured neurons against the cytotoxicity of glutamate, nitric oxide, and oxidative stress. METHODS: Primary cultures of neonatal rat cardiac myocytes were exposed to oxidative stress (H2O2, 100 micromol/l) to induce cell death. Effects of SFA were evaluated with a number of markers of cell death. RESULTS: Pretreatment with SFA (100 micromol/l) significantly suppressed markers of cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and cell viability assay. Loss of mitochondrial membrane potential (DeltaPsi(m)) is a critical step of the death pathway, which is triggered by matrix calcium overload and reactive oxygen species. Serofendic acid prevented the DeltaPsi(m) loss induced by H2O2 in a concentration-dependent manner (with saturation by 100 micromol/l). Serofendic acid remarkably suppressed the H2O2-induced matrix calcium overload and intracellular accumulation of reactive oxygen species. The protective effect of SFA was comparable to that of a mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channel opener, diazoxide. Furthermore, mitoK(ATP) channel blocker, 5-hydroxydecanoate (500 micromol/l), abolished the protective effect of SFA. Co-application of SFA (100 micromol/l) and diazoxide (100 micromol/l) did not show an additive effect. Thus, SFA inhibited the oxidant-induced mitochondrial death pathway, presumably through activation of the mitoK(ATP) channel. CONCLUSIONS: Serofendic acid protects cardiac myocytes against oxidant-induced cell death by preserving the functional integrity of mitochondria.
OBJECTIVES: We examined whether serofendic acid (SFA) has protective effects against oxidative stress in cardiac myocytes. BACKGROUND: We previously identified a novel endogenous substance, SFA, from a lipophilic extract of fetal calf serum. Serofendic acid protects cultured neurons against the cytotoxicity of glutamate, nitric oxide, and oxidative stress. METHODS: Primary cultures of neonatal rat cardiac myocytes were exposed to oxidative stress (H2O2, 100 micromol/l) to induce cell death. Effects of SFA were evaluated with a number of markers of cell death. RESULTS: Pretreatment with SFA (100 micromol/l) significantly suppressed markers of cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and cell viability assay. Loss of mitochondrial membrane potential (DeltaPsi(m)) is a critical step of the death pathway, which is triggered by matrix calcium overload and reactive oxygen species. Serofendic acid prevented the DeltaPsi(m) loss induced by H2O2 in a concentration-dependent manner (with saturation by 100 micromol/l). Serofendic acid remarkably suppressed the H2O2-induced matrix calcium overload and intracellular accumulation of reactive oxygen species. The protective effect of SFA was comparable to that of a mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channel opener, diazoxide. Furthermore, mitoK(ATP) channel blocker, 5-hydroxydecanoate (500 micromol/l), abolished the protective effect of SFA. Co-application of SFA (100 micromol/l) and diazoxide (100 micromol/l) did not show an additive effect. Thus, SFA inhibited the oxidant-induced mitochondrial death pathway, presumably through activation of the mitoK(ATP) channel. CONCLUSIONS:Serofendic acid protects cardiac myocytes against oxidant-induced cell death by preserving the functional integrity of mitochondria.