title: Effects of sodium bisulfite with or without procaine derivatives on axons of cultured mouse dorsal root ganglion neurons.
abstract: OBJECTIVE
  Sodium bisulfite (NaHSO3) was clinically used as a preservative agent for local anesthetics but was later suspected to be neurotoxic. However, recent studies reported that NaHSO3 reduces the neurotoxicity of local anesthetics. The purpose of this study was to examine the effects of NaHSO3 with and without procaine on axonal transport in cultured mouse dorsal root ganglion (DRG) neurons.
  
  
  METHODS
  Experiment 1 served to determine the dose-dependent effects of NaHSO3 on axonal transport (DRG neurons were treated with 0.01, 0.1, 1, 10, or 20 mM of NaHSO3), whereas experiment 2 investigated the effect of 0.1 mM NaHSO3 on the action of local anesthetics on axonal transport (DRG neurons were treated with 1 mM procaine alone, or with 0.1 mM NaHSO3 plus 1 mM procaine). As an additional experiment, DRG neurons were also treated with 1 mM chloroprocaine alone, or with 0.1 mM NaHSO3 plus 1 mM chloroprocaine. In these experiments, we analyzed the percent change in the number of anterogradely and retrogradely transported organelles and recorded changes in neurite morphology using video-enhanced microscopy.
  
  
  RESULTS
  In experiment 1, NaHSO3 at more than 1 mM caused cell membrane damage and complete inhibition of axonal transport, whereas 0.1 mM NaHSO3 maintained axonal transport at 40% to 60% of control with intact cell membrane. In experiment 2, 1 mM procaine alone maintained axonal transport at 90% to 100%. However, application of 1 mM procaine-0.1 mM NaHSO3 solution resulted in deformation of neurites and with complete cessation of axonal transport. Likewise, although 1 mM chloroprocaine maintain axonal transport at 80% to 100%, 1 mM chloroprocaine-0.1 mM NaHSO3 arrested axonal transport.
  
  
  CONCLUSIONS
  NaHSO3 resulted in a dose-dependent damage to the cell membrane and axonal transport, especially when used in combination with procaine or chloroprocaine.
authors.affiliation: From the Departments of *Anesthesiology, and †Physiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Tamie
authors.initials: T
authors.lastname: Takenami
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hiruma
authors.forename: Haruka
authors.initials: H
authors.lastname: Kaneko
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011343:Procaine / Q000008:administration & dosage*; D013447:Sulfites / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D004338:Drug Combinations; D013447:Sulfites; D011343:Procaine; C009279:sodium bisulfite