N-Acetylcysteine protects against bupivacaine-induced myotoxicity caused by oxidative and sarcoplasmic reticulum stress in human skeletal myotubes
2010
Galbes , Olivier (INRA , Montpellier (France). UMR 0866 Différenciation Cellulaire et Croissance) | Bourret , Annick (Institut National de la Santé et de la Recherche Médicale(France). ERI25, “Muscle and Pathologies”; Université Montpellier 1, Unité Formation et de Recherche (UFR) Médecine) | Nouette-Gaulain , Karine (Université Bordeaux 2Institut National de la Santé et de la Recherche MédicaleCentre Hospitalier Universitaire de Bordeaux(France). Laboratoire de Physiopathologie Mitochondriale, Université Victor SegalenU688Pôle d’Anesthésie Réanimation, Hôpital Pellegrin) | Pillard , Fabien (Centre Hospitalier Universitaire de Toulouse(France). Service de la Fonction Respiratoire et de la Médecine du Sport, Hôpital Larrey) | Matecki , Stefan (Centre Hospitalier Universitaire de MontpellierInstitut National de la Santé et de la Recherche MédicaleUniversité Montpellier 1(France). Service de Physiologie Clinique, Hôpital A. de VilleneuveERI25, “Muscle et Pathologies”UFR Médecine, EA4202) | Py , Guillaume (INRA , Montpellier (France). UMR 0866 Différenciation Cellulaire et Croissance) | Mercier , Jacques (Institut National de la Santé et de la Recherche MédicaleCentre Hospitalier Universitaire de Montpellier(France). ERI25, “Muscle and Pathologies”; Université Montpellier 1, UFR Médecine, EA4202Service de Physiologie Clinique, Hôpital A. de Villeneuve) | Capdevila , Xavier (Institut National de la Santé et de la Recherche MédicaleCentre Hospitalier Universitaire de Montpellier(France). ERI25, “Muscle and Pathologies"Service d’Anesthésie et de Réanimation A, Hôpital Lapeyronie) | Philips , Alexandre (Institut National de la Santé et de la Recherche Médicale(France). ERI25, “Muscle and Pathologies")
* 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.
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