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

Authors

  • Shahdevi Nandar Kurniawan Neurology Department, Faculty of Medicine Brawijaya University, Malang, Indonesia
  • Muthia Marwah Neurology Department, Faculty of Medicine Brawijaya University, Malang, Indonesia
  • Rodhiyan R Neurology Department, Faculty of Medicine Brawijaya University, Malang, Indonesia
  • Nanik S Public Health Department, Faculty of Medicine Brawijaya University, Malang, Indonesia

DOI:

https://doi.org/10.29121/granthaalayah.v8.i2.2020.214

Keywords:

Nimodipine, NRF2, NF-kB, Hyperglycemia, SH-SY5Y

Abstract [English]

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.

Downloads

Download data is not yet available.

References

Bhakkiyalakshmi E, Sireesh D, Rajaguru P, Paulmurugan R, Ramkumar KM. The emerging role of redox-sensitive Nrf2–Keap1 pathway in diabetes. Pharmacol Res, 2015, 91:104–114.

Jiang, T. et al. The protective role of Nrf2 in STZ-induced diabetic nephropathy. Progress in physiology. 2010, 41(6), pp. 435–438.

Kappelle, A. C. et al. Beneficial effect of the Ca2+ antagonist, nimodipine, diabetic neuropathy in the BB / Wor rat existing. 1994, pp. 887–893.

Kumar, A. and Mittal, R. Nrf2: a potential therapeutic target for diabetic neuropathy, Inflammopharmacology. Springer International Publishing. 2017, 25(4), pp. 393–402.

Ma, Q. HHS Public Access, Annual Review of Pharmacology and Toxicology. 2015, (1), pp. 401–426.

Negi, C. K. and Jena, G. Nrf2, a novel molecular target to reduce type 1 diabetes associated secondary complications: The basic considerations, European Journal of Pharmacology. Elsevier B.V. 2019, 843, pp. 12–26.

Neurology, A. A. Treatment of painful neuropathy, 2007, pp. 531–535.

Oyenihi, A. B. et al. Antioxidant strategies in the management of diabetic neuropathy, BioMed Research International. Hindawi Publishing Corporation, 2015.

Russell, J. W. et al. High glucose-induced oxidative stress and mitochondrial dysfunction in neurons, FASEB Journal. 2002, 16, p. 1742.

Schroeder, T., Hamilton, K. and Irwin, D. C. NIH Public Access. 2014, pp. 264–273.

Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, S. S. Buku Ajar Ilmu Penyakit Dalam. jilid II. Jakarta: Interna Publishing. 2009.

Verkhratsky, A. and Fernyhough, P. Calcium signalling in sensory neurones and peripheral glia in the context of diabetic neuropathies, Cell Calcium. Elsevier Ltd, 2014, 56(5), pp. 362–371.

Vetter, I. and Lewis, R. J. (2010) ‘Characterization of endogenous calcium responses in neuronal cell lines’, Biochemical Pharmacology, 79(6), pp. 908–920. doi: 10.1016/j.bcp.2009.10.020.

Vinik, A. et al. Diabetic neuropathies: Clinical manifestations and current treatment options, Nature Clinical Practice Endocrinology and Metabolism. 2006, 2(5), pp. 269–281.

Uguz A. C., Naziroglu M., Espino J., Bejarano I., Gonzalez D., Rodri- guez A. B. and Pariente J. A. Selenium modulates oxidative stress-induced cell apoptosis in human myeloid HL-60 cells through regulation of calcium release and caspase-3 and -9 activities. J. Membr. Biol. 2009, 232, 15–23.

Zhang, D. D. et al. The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus, Molecular and cellular biology. 2017, 7(11), pp. 769–789.

Downloads

Published

2020-02-29

How to Cite

Kurniawan, S. N., Marwah, M., R, R., & S, N. (2020). THE EFFECT OF 500 NM DOSAGE OF NIMODIPINE ON NRF2 AND NF-KB EXPRESSION IN NEURON CELL LINE CULTURE SH-SY5Y EXPOSED WITH CHRONIC HYPERGLYCEMIA. International Journal of Research -GRANTHAALAYAH, 8(2), 235–242. https://doi.org/10.29121/granthaalayah.v8.i2.2020.214