Effect of Sugammadex and Rocuronium Combination on Cranial Neurotoxicity in Rats: Experimental Study

Sugammadex is frequently used in clinical anesthetic practice. In order to determine whether sugammadex has neurotoxic effect, histopathological evaluation and antioxidant status of brain and cerebellum tissues were investigated. Thirty-two adult sprague dawley rats were divided into four groups. Purine Control Group (Group 1, n=8) had no action. The control group (Group 2, n=8) received 16 mg/ kg serum physiologic, the sugammadex group (Group 3, n=8) received 16 mg/kg sugammadex and the sugammadex+rocuronium group (Group 4, n=8) received 16 mg/kg sugammadex and 1 mg/kg rocuronium. After drug administration, brain and cerebellum tissues were evaluated histological and biochemically for and oxidative damage. The overall structure of the brain and cerebellum tissues were normal in all groups. Images of the layers and the neurons contained there in were normal. No pathological findings were found. There had no statistically significant diffrence between the groups in terms of glutathione enzyme activity levels (GSH-Px) and the malondialdehyde (MDA) levels in rat brain. GSH-Px and MDA levels had a slight increase in sugammadex and sugammadex+rocuronium group in cerebellum tissues. These increases were statistically significant. But this increase did not cause any histopathological damage to the cerebellum tissue. The study demonstrates that sugammadex is safe for reversal of rocuronium effcts in rats. Sugammadex in the dose ranges used in the studies, did not produce adverse effcts in rats brain and cerebellum tissues.

Ratlarda Sugammadex ve Rocuronium Kombinasyonunun Kraniyal Nörotoksisite Üzerine Etkisi: Deneysel Çalışma

Sugammadeks klinik anestezi uygulamalarında sıklıkla kullanılır. Sugammadeksin nörotoksik etkiye sahip olup olmadığını belirlemek için, beyin ve serebellum dokularının histopatolojik değerlendirmesi ve antioksidan durumu araştırıldı. Otuz iki erişkin sprague dawley sıçanı dört gruba ayrıldı. Purin Kontrol Grubuna (Grup 1, n=8) işlem yapılmadı. Kontrol grubuna (Grup 2, n=8) 16 mg/kg serum fizyolojik verildi. Sugammadex grubuna (Grup 3, n=8) 16 mg/kg sugammadex ve sugammadex+rocuronium grubuna (Grup 4, n=8) 16 mg/kg sugammadeks ve 1 mg/kg rokuronyum verildi. İlaç uygulamalarından sonra beyin ve beyincik dokuları histolojik ve oksidadif hasar açısından biyokimyasal olarak değerlendirildi. Beyin ve beyincik dokusunun genel yapısı tüm gruplarda normaldi. Katmanların ve içerdiği nöronların görüntüleri normaldi. Patolojik bulgu bulunamadı. Gruplar arasında sıçan beyninde glutatyon enzim aktivite düzeyleri (GSH-Px) ve malondialdehit (MDA) düzeyleri açısından istatistiksel olarak anlamlı bir fark yoktu. Serebellum dokularında GSH-Px ve MDA düzeyleri sugammadeks ve sugammadeks+rocuronium grubunda hafif bir artış gösterdi. Bu artışlar istatistiksel olarak anlamlıydı. Ancak bu artış, beyincik dokusunda histopatolojik hasara neden olmadı. Çalışma, sugammadeksin sıçanlarda rocuronyum etkisinin tersine çevrilmesinde güvenli olduğunu göstermektedir. Çalışmada kullanılan doz aralıklarında sugammadeks sıçan beyni ve beyincik dokularında olumsuz etki oluşturmamıştır.

Kaynakça

1. Lien CA: Development and potential clinical impairment of ultrashort-acting neuromuscular blocking agents. Br J Anaesth, 107 (1): i60-i71, 2011. DOI: 10.1093/bja/aer341

2. de Boer HD, van Egmond J, van de Pol F, Bom A, Booij LHDJ: Chemical encapsulation of rocuronium by synthetic cyclodextrin derivatives: Reversal of neuromuscular block in anaesthetized Rhesus monkeys. Br J Anaesth, 96 (2): 201-206, 2006. DOI: 10.1093/bja/aei306

3. Türk R, Kaya S, Dönmez İ, Özaydın İ, Merhan O, Yayla S, Ermutlu CŞ, Kaçar C, Aydın U, Aksoy Ö, Hüseyinoğlu Ü: The effct of rocuronium and sugammadex on progesterone levels in pregnant rabbits under general anesthesia. Kafkas Univ Vet Fak Derg, 25 (2): 179-184, 2019. DOI: 10.9775/kvfd.2018.20609

4. Naguib M: Sugammadex: Another milestone in clinical neuromuscular pharmacology. Anesth Analg, 104 (3): 575-581, 2007. DOI: 10.1213/01. ane.0000244594.63318.fc

5. 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, 8:CD012763, 2017. DOI: 10.1002/14651858.CD012763

6. Cammu G, De Kam PJ, Demeyer I, Decoopman M, Peeters PA, Smeets JM, Foubert L: Safety and toler-ability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers. Br J Anaesth, 100 (3): 373-379, 2008. DOI: 10.1093/bja/aem402

7. Pühringer FK, Rex C, Sielenkämper AW, Claudius C, Larsen PB, Prins ME, Eikermann M, Khuenl-Brady KS: Reversal of profound, highdose rocuronium-induced neuromuscular blockade by sugammadex at two diffrent time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology, 109 (2): 188-197, 2008. DOI: 10.1097/ALN.0b013e31817f5bc7

8. Marrocco I, Altieri F, Peluso I: Measurement and clinical significance of biomarkers of oxidative stress in humans. Oxid Med Cell Longev, 2017:6501046, 2017. DOI: 10.1155/2017/6501046

9. Srivastava KK, Kumar R: Stress, oxidative ınjury and disease. Indian J Clin Biochem, 30 (1): 3-10, 2015. DOI: 10.1007/s12291-014-0441-5

10. Mitchell C, Lobaz S: An overviev of sugammadex. Anaesthesia Tutorial of the Week. 1-6, 2016.

11. Palanca JM, Aguirre-Rueda D, Granell MV, Aldasoro M, Garcia A, Iradi A, Obrador E, Mauricio MD, Vila J, Gil-Bisquert A, Valles SL: Sugammadex, a neuromuscular blockade reversal agent, causes neuronal apoptosis in primary cultures. Int J Med Sci, 10 (10): 1278-1285, 2013. DOI: 10.7150/ijms.6254

12. Uludağ Ö: Hayvan deneyi çalışmalarında etik kuralların tarihçesi ve önemi. Adıyaman Üniv Sağlık Bil Derg, 5 (1): 1401-1413, 2019. DOI: 10.30569/adiyamansaglik.482098

13. Uchiyama M, Mihara M: Determination of malonaldehyde precursor in tissue by TBA test. Anal Biochem, 86 (1): 271-278, 1978. DOI: 10.1016/0003- 2697(78)90342-1

14. Elman GL: Tissue sulphydryl groups. Arch Biochem Biophys, 82 (1): 70- 77, 1959. DOI: 10.1016/0003-9861(59)90090-6

15. Kovac AL: Sugammadex: The first selective binding reversal agent for neuromuscular block. J Clin Anesth, 21 (6): 444-453, 2009. DOI: 10.1016/j. jclinane.2009.05.002

16. 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, 1298, 178-185, 2009. DOI: 10.1016/j.brainres.2009.08.037

17. Frank C, Rufini S, Tancredi V, Forcina R, Grossi D, D’Arcangelo G: Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus. Exp Neurol, 212 (2): 407-414, 2008. DOI: 10.1016/j.expneurol.2008.04.019

18. Abulrob A, Tauskela JS, Mealing G, Brunette E, Faid K, Stanimirovic D: Protection by cholesterol-extracting cyclodextrins: A role for N-methylD-aspartate receptor redistribution. J Neurochem, 92 (6): 1477-1486, 2005. DOI: 10.1111/j.1471-4159.2005.03001.x

19. Rivers JR, Maggo SDS, Ashton JC: Neuroprotective effct of hydroxypropyl-b-cyclodextrin in hypoxia-ischemia. Neuroreport, 23 (3): 134-138, 2012. DOI: 10.1097/WNR.0b013e32834ee47c

20. Ozbilgin S, Yılmaz O, Ergur BU, Hancı V, Ozbal S, Yurtlu S, Gunenc SF, Kuvaki B, Kucuk BA, Sisman AR: Effctiveness of sugammadex for cerebral ischemia/reperfusion injury. Kaohsiung J Med Sci, 32 (6): 292-301, 2016. DOI: 10.1016/j.kjms.2016.05.002

21. Baykal M, Gökmen N, Doğan A, Erbayraktar S, Yılmaz O, Ocmen E, Erdost HA, Arkan A: The effcts of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose. Braz J Anesthesiol, 67 (1): 1-5, 2017. DOI: 10.1016/j.bjane.2015.02.010

22. Savarese JJ, Caldwel JE, Lien CA, Miller RD: Pharmacology of muscle relaxants and their antagonists. In, Miller RD (Ed): Anesthesia. 5 th ed., 412-490, Churchill Livingstone, Philadelphia, 2000.

23. Lobaz S, Clymer M, Sammut M: Safety and efficacy of sugammadex for neuromuscular blockade reversal. Clin Med Insights Ther, 6 (2): 1-14, 2014. DOI: 10.4137/CMT.S10241

24. Aldasoro M, Jorda A, Aldasoro C, Marchio P, Guerra-Ojeda S, Gimeno-Raga M, Mauricio MD, Iradi A, Obrador E, Vila J, Valles SL: Neuronal effcts of sugammadex in combination with rocuronium or vecuronium. Int J Med Sci, 14 (3): 224-230, 2017. DOI: 10.7150/ijms.17545

25. Guang H, Ji L: Proprioceptive recognition with artificial neural networks based on organizations of spinocerebellar tract and cerebellum. Int J Neural Syst, 9:1850056, 2018. DOI: 10.1142/S0129065718500569

Kaynak Göster

658 317

Arşiv
Sayıdaki Diğer Makaleler

The Effect of Testosterone Supplementation on Capillar Morphometry and VEGF Expression Level of the Heart in Aged Mice

İLKNUR DABANOĞLU, BÜLENT BOZDOĞAN, ŞADİYE KUM

The Effect of the Supplemental Feeding of Queen Rearing Colonies on the Reproductive Characteristics of Queen Bees (Apis mellifera L.) Reared from Egg and Diffrent old of Larvae

MAHİR MURAT CENGİZ, KEMAL YAZICI, Servet ARSLAN

Diagnosis of Multiple Congenital Cardiac Defects in a Newborn Calf

MERİÇ KOCATÜRK, Volkan YAZICIOĞLU, HAKAN SALCI, ERSOY BAYDAR, ZEKİ YILMAZ

The Effects of Androctonus crassicauda Venom on Pregnant Rats and Their Offprings

Şule ÖZEL, MÜRŞİDE AYŞE DEMİREL, Nilüfer ERCAN, ÖZCAN ÖZKAN

Effects of Deep-Frying Sunflower Oil on Sperm Parameters in A Mouse Model: Do Probiotics Have A Protective Effct?

Serkan SAYINER, Nurhayat GÜLMEZ, Zafer SABİT, Murat GÜLMEZ

Genotoxic and Toxicopathological Effct of Afltoxin B1 in Grass Carp (Ctenopharyngodon idella)

Hayatullah KHAN, Farhan Anwar KHAN, Umar SADIQUE, Shakoor AHMAD, Zahoor Ul HASSAN, Faisal AHMAD, Abdul AHAD, Muqader SHAH, Ijaz AHMAD, Zahir SHAH, Zia-ur REHMAN

Brucella suis S2 Isolated from Aborted Sheep Fetuses in Northwestern China

Huan ZHANG, Benben WANG, Jihai YI, Zhen WANG, Junbo ZHANG, Yuanzhi WANG, Chuangfu CHEN

Present and Future Implications of Crimean Congo Haemorrhagic Fever Disease Emergence in Turkey

Atila T. KALAYCIOĞLU

Effect of Sugammadex and Rocuronium Combination on Cranial Neurotoxicity in Rats: Experimental Study

ÖZNUR ULUDAĞ

Evaluation of the Feasibility, Reversibility and Cardiorespiratory Effcts of Epidural Dexmedetomidine in Sedated Dogs Undergoing Orchiectomy

Hadi IMANI RASTABI, Hadi NADDAF, Bahman MOSALLANEJAD, Ahmad KHAJEH