Improvement of Screening for Protective Substances against Zinc-induced Neuronal Cell Death

Abstract

The inter-neuronal movement of zinc ions is a key mechanism involved in ischemic neuronal death. Therefore, zinc-induced neuronal cell death is a suitable phenomenon to observe for examining the neurodegenerative damage following ischemia. We have established a convenient and rapid screening system for protective substances against zinc-induced neuronal cell death and isolated carnosine, pyruvate, α-tocopherol, and gadolinium as protective substances. In this study, we modified the screening system to particularly identify substances with weak protective activity. The modifications, earlier administration of the samples and zinc, and the measurement of cell mortality, allowed the present assay to perform the sensitive and reliable detection of protective activity against zinc-induced GT1-7 cell death. Dose-dependency of pyruvate showed that the present assay was improved specially in detecting weak protective activity compared to the previous one. Using the present assay, numerous protective activities could be significantly distinguished from the real samples. The screening method with the present assay will extend the possibilities of screening samples.