Effects of levosimendan on the NB2A cell culture line

Aim: The aim of this project is to explore whether the levosimendan (LVS) has the neurotoxic effect on mouse neuroblastoma cancer cell lines (NB2a). It's known that the LVS effects through various mechanisms. It's also very well known that LVS inhibits Phosphodiesterase III and opens the ATP-sensitive K+ channels (KATP ), so it has the cardioprotective effect. Levosimendan strengthen contractions of myocardium without increasing consumption of oxygen and it is anti-oxidant, anti-inflammatory, inotropic and vasodilatory. Levosimendan is preferred to use in patients who have decreased ejection fraction during cardiac surgery. It is shown that LVS protects neurons indirectly, but it doesn't know the effect on neurons directly. In the present study, we examined whether Levosimendan has neurotoxic effects using neuroblastoma cell line of mouse origin (NB2a). Material and Method: For this aim, the toxic effects of LVS (0,1, 0,3, 1, 3, 10, 30 ve 100 µM) has been tested by Neurotoxicity Screening Test (NST) and apoptotic effects of LVS has been tested TUNEL method and MTT cell viability test. Results: There were no descript moderate neurotoxic effects in all concentrations ( 0,1, 0,3, 1, 3, 10, 30 ve 100 µM), on NTT test. Additionally, LVS with 1 µM concentration didn't inhibit the neuritis and also it significantly increased the length of neuritis. Levosimendan didn't affect the cell proliferation negatively and the number of apoptotic cells didn't different than those control cells (p>0.05). Conclusion: These direct neuroprotective effects of LVS might be explained by the hypothesis that LVS effects positively on ATP-sensitive K+ channels and adjusts the mechanisms of genetic transcription. Additionally, LVS has neuronal protective effect by inhibiting Phosphodiesterase III and decreasing exaggerated Ca 2+ influx. Levosimendan is especially preferred in patients who have decreased ejection fraction during cardiac surgery. Levosimendan can use securely in patients that have a risk of a brain injury due to the nature of the disease or the procedure itself. Keywords : Neurotoxicity, in vitro, levosimendan, NB2a, MTT