Screening of novel neuroprotective and neurotoxic compounds with the RT-CES technique
In recent years, a new cell-based high throughput paradigm has emerged, which seeks to identify novel, pharmacologically active neuroprotective and neurotoxic compounds. The essence of this approach is to create experimental models of cell injury relevant for a particular disease by establishing in vitro cell-based models, followed by high-throughput testing of compounds that affect the cellular response in a desired manner. Prior approaches typically used simple end-point analyses. To assess the neuro/cytoprotective and neurotoxic effects of novel drug candidates in real-time, we have applied a cell-microelectronic sensing technique (RT-CES), which measures changes in the impedance of individual microelectronic wells that correlates linearly with cell index (reflecting cell number, adherence and cell growth), thereby allowing the continuous determination of cell viability during oxidative stress. During the cytoprotective screenings in vitro cytotoxicity was elicited by hydrogen peroxide in primary rat neuronal cultures, neurone and hippocampal cell lines. Cells were post-treated at 30 min with various reference molecules and novel cytoprotective compounds. Cytotoxicity screenings were performed on several glioblastoma cell lines with treatment of cytotoxic compounds at different concentrations. Cytoprotection detected in the RT-CES system correlated well with the results of two classical end-point-based methods (improvement in MTT and reduction of LDH release). The rate of cell index decreased dose-dependently in cytotoxicity measurements and was proportional to the results of classical cell viability assays. The RT-CES method, when used as described in the current report, is suitable for the screening of molecular libraries to identify molecules or molecule combinations that attenuate oxidative stress-induced cell damage and can also be useful for screening of agents with antitumor properties.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Poster Presentation
Topic:
Disorders of the nervous system
Citation:
Ózsvári
B,
Nagy
LI and
Puskás
LG
(2010). Screening of novel neuroprotective and neurotoxic compounds with the RT-CES technique.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00055
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Received:
20 Apr 2010;
Published Online:
20 Apr 2010.
*
Correspondence:
Béla Ózsvári, Avidin Ltd, Szeged, Hungary, bela@avidinbiotech.com