title: N-acetylcysteine protects against bupivacaine-induced myotoxicity caused by oxidative and sarcoplasmic reticulum stress in human skeletal myotubes.
abstract: BACKGROUND
  Local anesthetics offer the benefits of extended analgesia with greater patient satisfaction and faster rehabilitation compared with intravenous morphine. These benefits, however, can be offset by adverse iatrogenic muscle pain. Here, the authors investigate the mechanisms of local anesthetic-induced myotoxicity and assess the protective effect of N-acetylcysteine.
  
  
  METHODS
  The authors used primary cell cultures of human skeletal muscle myoblasts to study local anesthetic adverse effects. Production of reactive oxygen species was investigated in human skeletal myotubes by fluorescence microscopy. Expression of sarcoplasmic/endoplasmic reticulum stress markers and induction of apoptosis were followed by immunofluorescence and Western blot analysis. Finally, the effect of N-acetylcysteine on bupivacaine-induced myotoxicity was investigated in vitro.
  
  
  RESULTS
  Bupivacaine sequentially induced reactive oxygen species production, oxidative stress, sarcoplasmic/endoplasmic reticulum stress, and activation of caspases 9 and 7 in human differentiated myoblasts. These iatrogenic effects were prevented by N-acetylcysteine.
  
  
  CONCLUSIONS
  The authors demonstrated a protective effect of N-acetylcysteine against bupivacaine-induced sarcoplasmic/endoplasmic reticulum stress and apoptosis in primary human skeletal muscle cell.
authors.affiliation: Institut National de la Recherche Agronomique (INRA), UMR866, Differenciation Cellulaire et Croissance, Montpellier, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Galbes
authors.forename: Annick
authors.initials: A
authors.lastname: Bourret
authors.forename: Karine
authors.initials: K
authors.lastname: Nouette-Gaulain
authors.forename: Fabien
authors.initials: F
authors.lastname: Pillard
authors.forename: Stefan
authors.initials: S
authors.lastname: Matecki
authors.forename: Guillaume
authors.initials: G
authors.lastname: Py
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.forename: Xavier
authors.initials: X
authors.lastname: Capdevila
authors.forename: Alexandre
authors.initials: A
authors.lastname: Philips
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002045:Bupivacaine / Q000633:toxicity*; D002478:Cells, Cultured; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D000111:Acetylcysteine; D002045:Bupivacaine