N -Acetylcysteine Protects against Bupivacaine-induced Myotoxicity Caused by Oxidative and Sarcoplasmic Reticulum Stress in Human Skeletal Myotubes

Author:

Galbes Olivier1,Bourret Annick2,Nouette-Gaulain Karine3,Pillard Fabien4,Matecki Stefan5,Py Guillaume6,Mercier Jacques7,Capdevila Xavier8,Philips Alexandre9

Affiliation:

1. Research Fellow, Institut National de la Recherche Agronomique (INRA), UMR866, “Differenciation Cellulaire et Croissance,” Montpellier, France.

2. Technician, Institut National de la Santé et de la Recherche Médicale (INSERM), ERI25, “Muscle and Pathologies”; Université Montpellier 1, Unité Formation et de Recherche (UFR) Médecine, EA4202, Montpellier, France.

3. Assistant Professor of Anesthesiology, Laboratoire de Physiopathologie Mitochondriale, Université Victor Segalen Bordeaux 2, Bordeaux, France; INSERM U688, Bordeaux, France; Pôle d'Anesthésie Réanimation, Hôpital Pellegrin, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France.

4. Assistant Professor of Physiology, CHU de Toulouse, Service de la Fonction Respiratoire et de la Médecine du Sport, Hôpital Larrey, Toulouse, France.

5. Professor of Physiology, CHU de Montpellier, Service de Physiologie Clinique, Hôpital A. de Villeneuve, Montpellier, France; INSERM, ERI25, “Muscle et Pathologies”; Université Montpellier 1, UFR Médecine, EA4202, Montpellier, France.

6. Senior Researcher, INRA, UMR866, “Differenciation Cellulaire et Croissance”, Montpellier, France.

7. Professor of Physiology, INSERM, ERI25, “Muscle and Pathologies”; Université Montpellier 1, UFR Médecine, EA4202; Centre Hospitalier Universitaire (CHU) de Montpellier, Service de Physiologie Clinique, Hôpital A. de Villeneuve, Montpellier, France.

8. Professor of Anesthesiology, INSERM, ERI25, “Muscle and Pathologies,” Montpellier, France; CHU de Montpellier, Service d'Anesthésie et de Réanimation A, Hôpital Lapeyronie, Montpellier, France.

9. Senior Researcher, INSERM, ERI25, “Muscle and Pathologies,” Montpellier, France.

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference33 articles.

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