Serofendic acid, a sulfur-containing diterpenoid derived from fetal calf serum, attenuates reactive oxygen species-induced oxidative stress in cultured striatal neurons

We previously identified a novel endogenous substance, serofendic acid, from a lipophilic extract of fetal calf serum. Serofendic acid protects cultured cortical neurons against the cytotoxicity of glutamate and nitric oxide. Here, we reported the protective effect of serofendic acid on reactive oxygen species-induced oxidative stress using primary rat striatal cultures. In addition, we compared the neuroprotective effect and the radical-scavenging activity of serofendic acid with those of dimethyl sulfoxide (DMSO), because serofendic acid possesses a DMSO structure. Paraquat caused neuronal death, which was inhibited by a cell-permeable superoxide dismutase (SOD) mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (Mn-TBAP); a cell-permeable SOD/catalase mimetic, EUK-134 [manganese 3-methoxy N,N′-bis(salicylidene) ethylenediamine chloride]; and a ferrous ion chelator, 2,2′-dipyridyl, in rat striatal cultures. Serofendic acid (10-100 μM) suppressed the neurotoxicity of paraquat, whereas DMSO (10-100 μM) did not. By contrast, higher concentrations (30-300 mM) of DMSO ameliorated the paraquat-induced cell death. Furthermore, H₂O₂ induced neurotoxicity, which was prevented by EUK-134 and 2,2′-dipyridyl. Serofendic acid (10-100 μM) also protected striatal neurons against the H₂O₂-induced toxicity. Higher concentrations (30-300 mM) of DMSO ameliorated H ₂O₂-induced neuronal death, whereas lower concentrations (10-100 μM) did not. Electron spin resonance spectrometry with a spin-trapping technique revealed that serofendic acid and DMSO had approximately the same ability to inhibit the formation of the hydroxyl radical (·OH). These results suggest that the ·OH-scavenging activity of serofendic acid is attributable to its DMSO structure and that the remaining components such as the atisane structure play an important role in eliciting neuroprotection at a concentration range of 10 to 100 μM.