Serofendic acid, a novel substance extracted from fetal calf serum, protects against oxidative stress in neonatal rat cardiac myocytes.

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.