Comparison of the cytotoxic, genotoxic and apoptotic effects of Sugammadex and Neostigmine on human embryonic renal cell (HEK-293)

Evren Büyükfırat; ć°smail Koyuncu; Mahmut Alp Karahan; Orhan Binici; Nuray Altay; Adnan Kirmit; Ataman Gönel

doi:10.14715/cmb/2018.64.13.14

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Vol. 64 No. 13: Issue 13

Issue Published : November 2, 2018

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Comparison of the cytotoxic, genotoxic and apoptotic effects of Sugammadex and Neostigmine on human embryonic renal cell (HEK-293)

https://doi.org/10.14715/cmb/2018.64.13.14

Evren Büyükfırat

Department of Anesthesiology and Reanimation, Harran University Medical Faculty, Åžanlıurfa, Turkey

ć°smail Koyuncu

Department of Medical Biochemistry, Harran University, Medical Faculty, Åžanlıurfa, Turkey

Mahmut Alp Karahan

Department of Anesthesiology and Reanimation, Harran University Medical Faculty, Åžanlıurfa, Turkey

Orhan Binici

Department of Anesthesiology and Reanimation, Harran University Medical Faculty, Åžanlıurfa, Turkey

Nuray Altay

Department of Anesthesiology and Reanimation, Harran University Medical Faculty, Åžanlıurfa, Turkey

Adnan Kirmit

Department of Medical Biochemistry, Harran University, Medical Faculty, Åžanlıurfa, Turkey

Ataman Gönel

Department of Medical Biochemistry, Harran University, Medical Faculty, Åžanlıurfa, Turkey

Corresponding Author(s) : Evren Büyükfırat

evrenbf@gmail.com

Cellular and Molecular Biology, Vol. 64 No. 13: Issue 13
Article Published : October 30, 2018

Abstract

Acetylcholinesterase inhibitors, including Neostigmine, have been used to reverse neuromuscular blockage for many years. Sugammadex reverses this blockage using its gamma cyclodextrin ring, a mechanism that differs from that of cholinesterases and so circumvents the side effects of Neostigmine. Although the superiority of Sugammadex to Neostigmine has been outlined in several clinical studies, to our knowledge, there is not any research into cell culture that compares the cytotoxic, genotoxic and apoptotic effects of the two drugs. Hence, this is the first study to compare the cytotoxic, genotoxic and apoptotic effects of different dosages of both drugs on human embryonic renal (HEK-293) cells. In this study, the cytotoxicity, genotoxicity and apoptotic effects of Sugammadex and Neostigmine on HEK-293 cells were analyzed with using the MTT, Comet Assay and Flow Cytometric Annexin-V methods, respectively. The results demonstrate that Neostigmine at 50, 100, 250, and 500 µg/mL is more cytotoxic than equivalent dosages of Sugammadex. Neostigmine at 500 and 1000 µg/mL was found to be more genotoxic, and Neostigmine at 500 µg/mL had a statistically higher risk of causing apoptosis and necrosis than Sugammadex (p<0.05). Neostigmine administered in-vitro in the same doses as Sugammadex had greater cytotoxic, genotoxic and apoptotic effects on HEK-293 cells.

Keywords

Anesthesia Apoptosis Cytotoxicity Genotoxicity HEK293 cells Neostigmine Sugammadex.

Büyükfırat, E., Koyuncu, ć°smail, Karahan, M. A., Binici, O., Altay, N., Kirmit, A., & Gönel, A. (2018). Comparison of the cytotoxic, genotoxic and apoptotic effects of Sugammadex and Neostigmine on human embryonic renal cell (HEK-293). Cellular and Molecular Biology, 64(13), 74–78. https://doi.org/10.14715/cmb/2018.64.13.14

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References

Fisher DM. Clinical pharmacology of neuromuscular blocking agents. Am J Health Syst Pharm. 1999;56:S4–9
Srivastava A, Hunter JM. Reversal of neuromuscular block. Br J Anaesth. 2009;103:115–29.
Bom A, Bradley M, Cameron K, Clark JK, Van Egmond J, Feilden H, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed Engl. 2002;41:266-70.
Wu X, Oerding H, Liu J, Vanacker B, Yao S, Dahl V, et al. Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects. BMC Anesthesiol. 2014;14:53.
Ozgün C, Cakan T, Baltacı B, Başar H. Comparison of reversal and adverse effects of sugammadex and combination of - Anticholinergic-Anticholinesterase agents in pediatric patients. J Res Med Sci. 2014;19:762-8.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55-63.
Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175:184-91.
Kocyigit A, Selek S, Celik H, Dikilitas M. Mononuclear leukocyte DNA damage and oxidative stress: the association with smoking of hand-rolled and filter-cigarettes. Mutat Res. 2011;721:136-41
Bom A, Hope F, Rutherford S, Thomson K. Preclinical pharmacology of sugammadex. J Crit Care. 2009;24:29-35.
Bom A, Bradley M, Cameron K, Clark JK, Van Egmond J, Feilden H, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed Engl. 2002;41:266-70.
Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Ostergaard D, Prins ME, et al. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006;104:667-74.
Challa R, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech. 2005;6:E329-57.
Rufini S, Grossi D, Luly P, Tancredi V, Frank C, D'Arcangelo G. Cholesterol depletion inhibits electrophysiological changes induced by anoxia in CA1 region of rat hippocampal slices. Brain Res 2009;1298:178e85.
Ozbilgin S, Yılmaz O, Ergur BU, Hancı V, Ozbal S, Yurtlu S, et al. Effectiveness of sugammadex for cerebral ischemia/reperfusion injury. Kaohsiung J Med Sci. 2016;32:292-301.
Qian J, Zhang JM, Lin LL, Dong WZ, Cheng YQ, Su DF, et al. A combination of neostigmine and anisodamine protects against ischemic stroke by activating Î±7nAChR. Int J Stroke. 2015;10:737-44.
Palanca JM, Aguirre-Rueda D, Granell MV, Aldasoro M, Garcia A, Iradi A, et al. Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures. Int J Med Sci. 2013;10:1278-85.
Buonanno P, Laiola A, Palumbo C, Spinelli G, Servillo G, Di Minno RM, et al. Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block. Anesth Analg. 2016;122:1826-30.

References

Fisher DM. Clinical pharmacology of neuromuscular blocking agents. Am J Health Syst Pharm. 1999;56:S4–9

Srivastava A, Hunter JM. Reversal of neuromuscular block. Br J Anaesth. 2009;103:115–29.

Bom A, Bradley M, Cameron K, Clark JK, Van Egmond J, Feilden H, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed Engl. 2002;41:266-70.

Wu X, Oerding H, Liu J, Vanacker B, Yao S, Dahl V, et al. Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects. BMC Anesthesiol. 2014;14:53.

Ozgün C, Cakan T, Baltacı B, Başar H. Comparison of reversal and adverse effects of sugammadex and combination of - Anticholinergic-Anticholinesterase agents in pediatric patients. J Res Med Sci. 2014;19:762-8.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55-63.

Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175:184-91.

Kocyigit A, Selek S, Celik H, Dikilitas M. Mononuclear leukocyte DNA damage and oxidative stress: the association with smoking of hand-rolled and filter-cigarettes. Mutat Res. 2011;721:136-41

Bom A, Hope F, Rutherford S, Thomson K. Preclinical pharmacology of sugammadex. J Crit Care. 2009;24:29-35.

Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Ostergaard D, Prins ME, et al. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006;104:667-74.

Challa R, Ahuja A, Ali J, Khar RK. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech. 2005;6:E329-57.

Rufini S, Grossi D, Luly P, Tancredi V, Frank C, D'Arcangelo G. Cholesterol depletion inhibits electrophysiological changes induced by anoxia in CA1 region of rat hippocampal slices. Brain Res 2009;1298:178e85.

Ozbilgin S, Yılmaz O, Ergur BU, Hancı V, Ozbal S, Yurtlu S, et al. Effectiveness of sugammadex for cerebral ischemia/reperfusion injury. Kaohsiung J Med Sci. 2016;32:292-301.

Qian J, Zhang JM, Lin LL, Dong WZ, Cheng YQ, Su DF, et al. A combination of neostigmine and anisodamine protects against ischemic stroke by activating Î±7nAChR. Int J Stroke. 2015;10:737-44.

Palanca JM, Aguirre-Rueda D, Granell MV, Aldasoro M, Garcia A, Iradi A, et al. Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures. Int J Med Sci. 2013;10:1278-85.

Buonanno P, Laiola A, Palumbo C, Spinelli G, Servillo G, Di Minno RM, et al. Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block. Anesth Analg. 2016;122:1826-30.

Author biographies is not available.