International Journal of Medical Sciences

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18 December 2017

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Int J Med Sci 2013; 10(10):1278-1285. doi:10.7150/ijms.6254

Research Paper

Sugammadex, a Neuromuscular Blockade Reversal Agent, Causes Neuronal Apoptosis in Primary Cultures

José M. Palanca1, Diana Aguirre-Rueda2, Manuel V. Granell1, Martin Aldasoro2, Alma Garcia2, Antonio Iradi2, Elena Obrador2, Maria Dolores Mauricio2, Jose Vila2, Anna Gil-Bisquert2, Soraya L. Valles2✉

1. Department of Surgery/Anaesthesiology, School of Medicine and Odontology, University of Valencia, Spain;
2. Department of Physiology, School of Medicine and Odontology, University of Valencia, Spain.

Abstract

Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system).

Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types.

Keywords: Sugammadex, apoptosis, CytC, AIF, Smac/Diablo and CASP-3.

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How to cite this article:
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 2013; 10(10):1278-1285. doi:10.7150/ijms.6254. Available from http://www.medsci.org/v10p1278.htm