THE EFFECT OF 500 NM DOSAGE OF NIMODIPINE ON NRF2 AND NFKB EXPRESSION IN NEURON CELL LINE CULTURE SH-SY5Y EXPOSED WITH CHRONIC HYPERGLYCEMIA

Introduction: Metabolic stress and mitochondrial dysfunction in chronic hyperglycemia can cause an increase in Ca2+ cytosol ions that cause dysfunction of NRF2, that will increase the activity of NF-kB which causes an increase in cytokine production, where NF-kB can modulate NRF2 transcription and its activity, so that it has positive or negative effects in the target gene. Giving nimodipine in chronic hyperglycemia conditions can increase levels of NRF2 molecules and reduce levels of NF-kB. Aim: The purpose of this research is to know the effect of treating nimodipine dose 5 μM towards expression of the protein NRF2and NF-kB in SH-SY5Y cell culture induced by chronic hyperglycemia. Method: This study is a true experimental study using randomized posttest only controlled group design in human SH-SY5Y neuron cell culture. Neuron cells were exposed with chronic glucose (25 mM / G25 normoglycemia, 50 mM / G50 hyperglycemia) for 6 days, followed by administration of nimodipine (without nimodipine and nimodipine 500 nM) for 30 minutes. Calculation of NRF2 and NF-kB expressions done by fluorescence method. Results: There were significant differences in the NF-kB neuron cells in the treatment group with controls, both normoglycemia and hyperglycemia (p <0.05). Nimodipine was not able to increase the expression of NRF-2 in the treatmnrnt group, although there were significance differences between these two groups. The Spearman Rank correlation test showed a negative correlation between NRF2 and NF-kB expression in the SH-SY5Y human cell line neuron culture that exposed to chronic hyperglycemia with administration of 500 nM nimodipine. Conclusion: There was a statistically significant decrease in NF-kB expression in SH-SY5Y neuron cells that exposed to chronic hyperglycemia given nimodipine compared to controls group. Nimodipine treatment to SH-SY5Y neuron cells exposed to hyperglycemia not yet increase expression of NRF2.