Sugammadex Causes C6 Glial Cell Death and Exacerbates Hydrogen Peroxide-Induced Oxidative Stress
Year 2022,
, 22 - 27, 30.03.2022
Bilal Şahin
,
Sabahattin Karabulut
Abstract
Objective: Sugammadex (SUG) quickly reverses steroidal neuromuscular blocking drugs after anesthesia. It has been reported that SUG has a toxic effect on neurons in primary culture. This study aims to examine the effect of SUG on glial cell viability, oxidative stress, and apoptosis in C6 glial cells after exposure to H2O2.
Method: In this study, C6 glioma cell line was used to study the effect of SUG on the glial cell in four cell groups. The control group was untreated. Cells in the H2O2group were treated with 0.5 mM H2O2 for 24 h. Cells in the SUG group were treated with 50 μg/mL SUG for 24 h. Cells in the SUG+ H2O2 group were pre-treated with 50 μg/mL of SUG for 1 h before 24-h exposure to 0.5 mM H2O2. Cell viability was evaluated using XTT assay. Total antioxidant status (TAS), total oxidant status (TOS), caspase-3, Bax, 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and cleaved-PARP levels in the cells were measured by commercial kits.
Results: SUG significantly decreased the viability of C6 cells after H2O2-induced oxidative stress (p < 0.05). SUG pretreatment also raised TOS levels and led to increased Bax, Caspase-3, 8-OHdG, and cleaved PARP levels after H2O2-induced oxidative damage in C6 cells (p < 0.05).
Thanks
We would like to thank the Sivas Cumhuriyet University, School of Medicine, CUTFAM Research Center, Sivas, Turkey, for providing the necessary facilities to conduct this study.
References
- 1. Stäuble CG, Blobner M. The future of neuromuscular blocking agents. Curr Opin Anaesthesiol. 2020;33(4):490-498. doi:10.1097/ACO.0000000000000891
- 2. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010;111(1):120-128. doi:10.1213/ANE.0b013e3181da832d
- 3. Karalapillai D, Kaufman M, Weinberg L. Sugammadex. Crit Care Resusc. 2013;15(1):57-62.
- 4. Hawkins J, Khanna S, Argalious M. Sugammadex for Reversal of Neuromuscular Blockade: Uses and Limitations. Curr Pharm Des. 2019;25(19):2140-2148. doi:10.2174/1381612825666190704101145
- 5. Sorgenfrei IF, Norrild K, Larsen PB, et al. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006;104(4):667-674. doi:10.1097/00000542-200604000-00009
- 6. de Boer HD, Driessen JJ, Marcus MA, Kerkkamp H, Heeringa M, Klimek M. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study. Anesthesiology. 2007;107(2):239-244.
doi:10.1097/01.anes.0000270722.95764.37
- 7. Sparr HJ, Vermeyen KM, Beaufort AM, et al. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics. Anesthesiology. 2007;106(5):935-943. doi:10.1097/01.anes.0000265152.78943.74
- 8. Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 2017;8(8):CD012763. doi:10.1002/14651858.CD012763
- 9. Honing G, Martini CH, Bom A, et al. Safety of sugammadex for reversal of neuromuscular block. Expert Opin Drug Saf. 2019;18(10):883-891. doi:10.1080/14740338.2019.1649393
- 10. Kovac AL. Sugammadex: the first selective binding reversal agent for neuromuscular block. J Clin Anesth. 2009;21(6):444-453. doi:10.1016/j.jclinane.2009.05.002
- 11. Lazo Uslar C, Navarro Vives L, Miquel Marco S, Roger Reig A, Basagaña Torrento M. Sugammadex Induced Anaphylaxis: Two Case Reports [published online ahead of print, 2021 Jun 15]. J Investig Allergol Clin Immunol. 2021;0. doi:10.18176/jiaci.0719
- 12. Palanca JM, Aguirre-Rueda D, Granell MV, et al. Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures. Int J Med Sci. 2013;10(10):1278-1285. Published 2013 Aug 3. doi:10.7150/ijms.6254
- 13. Wu YC, Sonninen TM, Peltonen S, Koistinaho J, Lehtonen Š. Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells. Int J Mol Sci. 2021;22(14):7710. Published 2021 Jul 19. doi:10.3390/ijms22147710
- 14. Chodobski A, Zink BJ, Szmydynger-Chodobska J. Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res. 2011;2(4):492-516. doi:10.1007/s12975-011-0125-x
- 15. Galea I. The blood-brain barrier in systemic infection and inflammation. Cell Mol Immunol. 2021;18(11):2489-2501. doi:10.1038/s41423-021-00757-x
- 16. Saunders NR, Knott GW, Dziegielewska KM. Barriers in the immature brain. Cell Mol Neurobiol. 2000;20(1):29-40. doi:10.1023/a:1006991809927
- 17. Erel, O. A Novel Automated Direct Measurement Method for Total Antioxidant Capacity Using a New Generation, More Stable ABTS Radical Cation. Clin. Biochem., 2004, 37(4), 277–85.
- 18. Erel, O. A New Automated Colorimetric Method for Measuring Total Oxidant Status. Clin. Biochem., 2005, 38(12), 1103–11.
- 19. Bom A, Hope F, Rutherford S, Thomson K. Preclinical pharmacology of sugammadex. J Crit Care. 2009;24(1):29-35. doi:10.1016/j.jcrc.2008.10.010
- 20. Jeyadoss J, Kuruppu P, Nanjappa N, Van Wijk R. Sugammadex hypersensitivity-a case of anaphylaxis. Anaesth Intensive Care. 2014;42(1):89-92. doi:10.1177/0310057X1404200115
- 21. Tauffenberger A, Magistretti PJ. Reactive Oxygen Species: Beyond Their Reactive Behavior. Neurochem Res. 2021;46(1):77-87. doi:10.1007/s11064-020-03208-7
- 22. Arslan B, Sahin T, Ozdogan H. Sugammadex and anaphylaxis: An analysis of 33 published cases. J Anaesthesiol Clin Pharmacol. 2021;37(2):153-159. doi:10.4103/joacp.JOACP_383_19
Year 2022,
, 22 - 27, 30.03.2022
Bilal Şahin
,
Sabahattin Karabulut
References
- 1. Stäuble CG, Blobner M. The future of neuromuscular blocking agents. Curr Opin Anaesthesiol. 2020;33(4):490-498. doi:10.1097/ACO.0000000000000891
- 2. Murphy GS, Brull SJ. Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010;111(1):120-128. doi:10.1213/ANE.0b013e3181da832d
- 3. Karalapillai D, Kaufman M, Weinberg L. Sugammadex. Crit Care Resusc. 2013;15(1):57-62.
- 4. Hawkins J, Khanna S, Argalious M. Sugammadex for Reversal of Neuromuscular Blockade: Uses and Limitations. Curr Pharm Des. 2019;25(19):2140-2148. doi:10.2174/1381612825666190704101145
- 5. Sorgenfrei IF, Norrild K, Larsen PB, et al. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006;104(4):667-674. doi:10.1097/00000542-200604000-00009
- 6. de Boer HD, Driessen JJ, Marcus MA, Kerkkamp H, Heeringa M, Klimek M. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study. Anesthesiology. 2007;107(2):239-244.
doi:10.1097/01.anes.0000270722.95764.37
- 7. Sparr HJ, Vermeyen KM, Beaufort AM, et al. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics. Anesthesiology. 2007;106(5):935-943. doi:10.1097/01.anes.0000265152.78943.74
- 8. Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 2017;8(8):CD012763. doi:10.1002/14651858.CD012763
- 9. Honing G, Martini CH, Bom A, et al. Safety of sugammadex for reversal of neuromuscular block. Expert Opin Drug Saf. 2019;18(10):883-891. doi:10.1080/14740338.2019.1649393
- 10. Kovac AL. Sugammadex: the first selective binding reversal agent for neuromuscular block. J Clin Anesth. 2009;21(6):444-453. doi:10.1016/j.jclinane.2009.05.002
- 11. Lazo Uslar C, Navarro Vives L, Miquel Marco S, Roger Reig A, Basagaña Torrento M. Sugammadex Induced Anaphylaxis: Two Case Reports [published online ahead of print, 2021 Jun 15]. J Investig Allergol Clin Immunol. 2021;0. doi:10.18176/jiaci.0719
- 12. Palanca JM, Aguirre-Rueda D, Granell MV, et al. Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures. Int J Med Sci. 2013;10(10):1278-1285. Published 2013 Aug 3. doi:10.7150/ijms.6254
- 13. Wu YC, Sonninen TM, Peltonen S, Koistinaho J, Lehtonen Š. Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells. Int J Mol Sci. 2021;22(14):7710. Published 2021 Jul 19. doi:10.3390/ijms22147710
- 14. Chodobski A, Zink BJ, Szmydynger-Chodobska J. Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res. 2011;2(4):492-516. doi:10.1007/s12975-011-0125-x
- 15. Galea I. The blood-brain barrier in systemic infection and inflammation. Cell Mol Immunol. 2021;18(11):2489-2501. doi:10.1038/s41423-021-00757-x
- 16. Saunders NR, Knott GW, Dziegielewska KM. Barriers in the immature brain. Cell Mol Neurobiol. 2000;20(1):29-40. doi:10.1023/a:1006991809927
- 17. Erel, O. A Novel Automated Direct Measurement Method for Total Antioxidant Capacity Using a New Generation, More Stable ABTS Radical Cation. Clin. Biochem., 2004, 37(4), 277–85.
- 18. Erel, O. A New Automated Colorimetric Method for Measuring Total Oxidant Status. Clin. Biochem., 2005, 38(12), 1103–11.
- 19. Bom A, Hope F, Rutherford S, Thomson K. Preclinical pharmacology of sugammadex. J Crit Care. 2009;24(1):29-35. doi:10.1016/j.jcrc.2008.10.010
- 20. Jeyadoss J, Kuruppu P, Nanjappa N, Van Wijk R. Sugammadex hypersensitivity-a case of anaphylaxis. Anaesth Intensive Care. 2014;42(1):89-92. doi:10.1177/0310057X1404200115
- 21. Tauffenberger A, Magistretti PJ. Reactive Oxygen Species: Beyond Their Reactive Behavior. Neurochem Res. 2021;46(1):77-87. doi:10.1007/s11064-020-03208-7
- 22. Arslan B, Sahin T, Ozdogan H. Sugammadex and anaphylaxis: An analysis of 33 published cases. J Anaesthesiol Clin Pharmacol. 2021;37(2):153-159. doi:10.4103/joacp.JOACP_383_19