serofendic-acid and pyrrolidine-2-4-dicarboxylic-acid

We have previously reported that a sulfur-containing neuroprotective substance named serofendic acid was purified and isolated from lipophilic extract of fetal calf serum (FCS). In the present study, we investigated the effect of serofendic acid on glutamate neurotoxicity using embryonic rat spinal cord culture. When cultures were exposed to glutamate (20 microM) with a glutamate transporter inhibitor L-trans-pyrrolidine-2,4-decarboxylate (PDC; 40 microM) for 24 h, motor neurons were injured through both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole/kainate receptors. This glutamate neurotoxicity was attenuated by nitric oxide (NO) synthase inhibitors. Serofendic acid (0.1-5 microM) prevented glutamate neurotoxicity in a concentration-dependent manner. S-Nitrosocysteine (SNOC; 10 microM), an NO donor, induced motor neuronal death. Serofendic acid (5 microM) also prevented SNOC-induced neurotoxicity. These results indicate that serofendic acid protects cultured motor neurons from glutamate neurotoxicity by reducing the cytotoxic action of NO.

Topics: Animals; Cell Survival; Cells, Cultured; Cysteine; Dicarboxylic Acids; Diterpenes; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Embryo, Mammalian; Glutamic Acid; Motor Neurons; Neuroprotective Agents; Neurotransmitter Uptake Inhibitors; Nitric Oxide Donors; Pyrrolidines; Rats; S-Nitrosothiols; Spinal Cord; Time Factors