Petr Mlejnek
Palacky University Olomouc, Czech Republic
Title: Cytotoxic agent, oxidative stress, N-acetylcysteine, cell death protection and overlooked chemistry behind
Biography
Biography: Petr Mlejnek
Abstract
Statement of the Problem: Many cytotoxic agents induce cell death that is accompanied by Reactive Oxygen Species (ROS) production and by Glutathione (GSH) depletion. Not surprisingly, N-Acetylcysteine (NAC), well known antioxidant and precursor of GSH synthesis, prevents the ROS production, restores GSH level and prevents cells from death. Such effect of NAC is usually used as corroborative evidence that, cell death induced by studied cytotoxic agent is mediated by ROS production and/or by GSH depletion. Detailed analysis of many experimental systems, however, shows that such simple interpretation of results might be misleading. The purpose of this study is to describe the general experimental approach as to how to avoid misinterpretation of the results.
Methodology: A detailed LC/MS/MS analysis of the possible interactions between studied cytotoxic agent and NAC within cells and in the growth medium was made.
Findings: We studied various compounds that are known to induce ROS production and/or GSH depletion prior to cell death induction and whose cytotoxicity can be abrogated by NAC. LC/MS/MS analysis revealed that NAC covalently bound to these compounds usually by non-enzymatic reaction and converted them into nontoxic compounds: Agent-NAC or agent-2NAC.
Conclusion & Significance: NAC is a reactive compound that may directly interact with the studied cytotoxic agent, while converting it into non-cytotoxic compound covalently bound with NAC.