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Volume 3, Issue 1 (Suppl) Toxicol Open Access
ISSN: 2476-2067 TYOA, an open access journal Toxicology Congress 2017
April 13-15, 2017
April 13-15, 2017 Dubai, UAE
8th World Congress on
Toxicology and Pharmacology
Cytotoxic agent, oxidative stress, N-acetylcysteine, cell death protection and overlooked chemistry behind
Petr Mlejnek
Palacky University Olomouc, Czech Republic
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.
Recent Publications
• Mlejnek P, Dolezel P and Kosztyu P (2012) P-glycoprotein mediates resistance to A3 adenosine receptor agonist 2-chloro-
N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide in human leukemia cells. J Cell Physiol 227: 676-685.
• Kosztyu P, Dolezel P and Mlejnek P (2013) Can P-glycoprotein mediate resistance to nilotinib in human leukaemia cells?
Pharmacol Res 67 (1): 79-83.
• Kosztyu P, Bukvova R, Dolezel P and Mlejnek P (2014) Resistance to daunorubicin, imatinib, or nilotinib depends on
expression levels of ABCB1 and ABCG2 in human leukemia cells. Chem Biol Interact 219: 203-210.
• Mlejnek P and Dolezel P (2014) N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin-N-
acetylcysteine adduct. Chem Biol Interact 220: 248-254.
• Mlejnek P and Dolezel P (2015) Loss of mitochondrial transmembrane potential and glutathione depletion are not
sufficient to account for induction of apoptosis by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone in human
leukemia K562 cells. Chem Biol Interact. 239: 100-110.
Biography
Petr Mlejnek is currently working as an Associate Professor in Biology and Head of the Department of Anatomy at the Palacky University in Olomouc, Czech
Republic. He completed his Master’s in Biochemistry from the University of J E Purkyne in Brno, Czech Republic and obtained his PhD degree in Biophysics from
the Institute of Biophysics Academy of Science of the Czech Republic in Brno, Czech Republic. He is a member of Scandinavian Society for Cell Toxicology and
International Society for the Study of Xenobiotics. Currently, he and his research group are focused on the study of mechanisms of cell death in cancer cells and
mechanisms of multidrug resistance in cancer cells.
Petr Mlejnek, Toxicol Open Access 2017, 3:1 (Suppl)