Effect of Low and High Dose Sugammadex on Erythrocyte Deformability in Streptozotocin-Induced Diabetic Rats

  • Hasan Ali Kiraz
  • Hüseyin Cihad Turgut
  • Seyfi Kartal
  • Faruk Metin Çomu
  • Gülay Kip
  • Metin Alkan
  • Muhammed Enes Aydın
  • Meral Erdal Erbatur
  • Mustafa Arslan Gazi Üniversitesi Tıp Fakültesi
  • Yusuf Ünal
Keywords: Erythrocyte deformability, diabetes, sugammadex, microcirculation


Objective: Erythrocyte deformability is a function of specially designed erythrocyte membrane properties and allows for the oxygen delivery without cell fragmentation. Impaired erythrocyte deformability in diabetes is one of the suspected factors that result in erythrocyte aggregation and the microvascular circulatory arrest. In this study, we aimed to investigate low versus high doses of sugammadex on erythrocyte deformability in streptozototocin-induced diabetic rats.Methods: Twenty-four male Wistar albino rats weighing between 225 and 300 gr were randomly divided into 4 groups. Group C (control; n=6), Group DC (diabetes control; n=6), Group DR-16S (diabetes-rocuronium-16mg sugammadex; n=6) and Group DR-96S (diabetes- rocuronium-96mg sugammadex; n=6). Rats in control and diabetes groups received a 0.9% NaCl solution at the same volume.  Diabetes was induced by a single IP injection of streptozotocin (Sigma Chemical, St. Louis, MO, USA) at a dose of 55 mg.kg-1 body weight, and animals were kept alive for 30 days. At the end of the follow-up period animals’ erythrocyte deformability was measured from blood samples.Results:  Serum glucose was significantly lower in Group C as compared to Groups DC, DR-16S and DR-96S (p<0.0001). The deformability index was significantly increased in the diabetic rats (p<0.0001).  It was significantly increased in Group DR-96S as compared to Group C and DC (p<0.0001, p=0.028, respectively).Conclusion: In this study, we showed the safety profile of low dose sugammadex in diabetic rats in terms of the erythrocyte deformability. Our findings may lead to future animal and human studies investigating sugammadex effects on erythrocyte deformability and micro/macrovascular circulation.


Chien S. Red cell deformability and its relevance to blood flow. Ann Rev Physiol 1987;49: 177-92.

Mchedlishvili G. Disturbed blood flow structuring as critical factor of hemorheological disorders in microcirculation. Clin Hemorheol Microcir 1998;19: 315-25.

Stoltz JF, Singh M, Riha P. Hemorheology in Practice (IOS Press, Amsterdam) 1999.

Mawatari S, Saito K, Murakami K, Fujino T. Absence of correlation between glycated hemoglobin and lipid composition of erythrocyte membrane in type 2 diabetic patients. Metabolism 2004;53:123-7.

Maksina AG, Mikaelian NP, Kniazev A, Dainiak BA. Structural changes in erythrocyte membranes in diabetes mellitus using spin labeled fatty acids. Biofizika 1992;37:306-9.

Jain SK, Mohandas N, Clark MR, Shohet SB. The effect of malonyldialdheide, a product of lipid peroxidation of the deformability, dehydration and Cr-survival of erythrocyte. Br J Haematol 1983;53:247-55.

Rizvi SI, Zaid MA, Anis R, Mishra N. Protective role of tea catechins against oxidation-induced damage of type 2 diabetic erythrocytes. Clin Experimen Pharmacol Physiol 2005;32:70-5.

Hayden MR, Tyagi SC, Kerklo M M, Nicolls MR. Type 2 Diabetes mellitus as a conormational disease. JOP 2005;6:287-302.

Pekpak M, Konukoğlu D, Ercan M, Erek E. Oxidative stress and trace elements in proteinuric patients. Office Journal of the Turkish Nephrology, Association 1999;4:213-8.

Schwartz RS, Madsen JW, Rybicki AC, Nagel RL. Oxidation of spectrin and deformability defects in diabetic erythrocytes. Diabetes 1991;40:701-8.

Gürbilek M, Dağlar C, Aköz M, Topçu C. Enzyme activity lipid peroxditaino and dhea(s) glucose and lipid levels in the diabetes mellitus patients. Turk J Biochem 2004;29:237-42.

Lawall H, Angelkort L. Correlation between rheological parameters and erythrocyte velocity in nailfold capillaries in patients with diabetes mellitus. Clin Hemorheol Microcirc 1999; 20:41-7.

Budak Y, Demirci H, Akdoğan M, Yavuz D. Erythrocyte membrane anionic charge in type 2 diabetic patients with retinopathy. BMC Ophthalmol 2004;4:14.

Barazzoni R, Kiwanuka E, Zanetti M, Cristini M, Vettore M, Tessari P. Insulin acutely increases fibrinogen production in individuals with type 2 diabetes but not in individuals without diabetes. Diabetes 2003; 52:1851-6.

Buder TF, Meistelman C, Raft J. Sugammadex: clinical development and practical use. Korean J Anesthesiol 2013;65:495-500.

Baldo B. Sugammadex and rocuronium-induced anaphylaxis. Anaesthesia 2012;67:1174-5

Raft J, Betala Belinga JF, Jurkolow G, Desandes E, Longrois D, Meistelman C. Clinical evaluation of post-surgical bleeding after a sugammadex injection. Ann Fr Anesth Reanim 2011;30:714-7.

Arslan M, Comu FM, Kip G, Alkan M, Kiraz HA, Ozer A, et al. Effect of dexmedetomidin on erythrocyte deformability during ischemia reperfusion injury of heart in diabetic rats. Bratisl Lek Listy 2014;115: 494-7.

Singh M, Shin S. Changes in erythrocyte aggregation and deformability in diabetes mellitus: A brief review. Indian J Exp Biol 2009;47:7-15.

Goldstein DE, Little RR, Wiedmeyer HM, England JD, McKenzie EM. Glycated hemoglobin: methodologies and clinical applications. Clin Chem 1986;32:B64-70.

Arslan M, Comu FM, Isık B, Ozturk K, Kesimer E. Effect of dexmedetomidine on erythrocyte deformability during ischemia reperfusion injury of liver in diabetic rats Bratisl Lek Listy 2012;113: 687-91.

Verando B, Fiorilli A, Croci G, Tringali C, Goi G, Mazzanti L, et al. Acidic and neutral sialidase in the erythrocyte membrane of type 2 diabetic patients. Blood 2002;99:1064-70.

Kowluru R, Bitensky MW, Kowluru A, Dembo M, Keaton PA, Buican T. Reversible sodium pump defect and swelling in the diabetic rat erythrocyte: effect of filterability and implications for microangiopathy. Proc Natl Acad Sci (USA) 1989;86:3327-31.

Original Research