title: Neuronal Effects of Sugammadex in combination with Rocuronium or Vecuronium.
abstract: Rocuronium (ROC) and Vecuronium (VEC) are the most currently used steroidal non-depolarizing neuromuscular blocking (MNB) agents. Sugammadex (SUG) rapidly reverses steroidal NMB agents after anaesthesia. The present study was conducted in order to evaluate neuronal effects of SUG alone and in combination with both ROC and VEC. Using MTT, CASP-3 activity and Western-blot we determined the toxicity of SUG, ROC or VEC in neurons in primary culture. SUG induces apoptosis/necrosis in neurons in primary culture and increases cytochrome C (CytC), apoptosis-inducing factor (AIF), Smac/Diablo and Caspase 3 (CASP-3) protein expression. Our results also demonstrated that both ROC and VEC prevent these SUG effects. The protective role of both ROC and VEC could be explained by the fact that SUG encapsulates NMB drugs. In BBB impaired conditions it would be desirable to control SUG doses to prevent the excess of free SUG in plasma that may induce neuronal damage. A balance between SUG, ROC or VEC would be necessary to prevent the risk of cell damage.
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Aldasoro
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Jorda
authors.affiliation: Hospital General de Castellon, Castellon, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Aldasoro
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Marchio
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Sol
authors.initials: S
authors.lastname: Guerra-Ojeda
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Gimeno-Raga
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Mª Dolores
authors.initials: MD
authors.lastname: Mauricio
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iradi
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Obrador
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jose Mª
authors.initials: JM
authors.lastname: Vila
authors.affiliation: Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Soraya L
authors.initials: SL
authors.lastname: Valles
mesh_terms: D000732:Androstanols / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis; D045304:Cytochromes c / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000009:adverse effects; D009474:Neurons / Q000187:drug effects*; D061251:Primary Cell Culture; D051381:Rats; D000077123:Rocuronium; D000077122:Sugammadex; D014673:Vecuronium Bromide / Q000008:administration & dosage*; D047408:gamma-Cyclodextrins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: C494831:Aifm1 protein, rat; D000732:Androstanols; D051033:Apoptosis Inducing Factor; D004338:Drug Combinations; D009466:Neuromuscular Blocking Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D014673:Vecuronium Bromide; D045304:Cytochromes c; D053148:Caspase 3; D000077123:Rocuronium
keywords: apoptosis.; neuron; rocuronium; sugammadex; vecuronium