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BJA Advance Access originally published online on August 30, 2009
British Journal of Anaesthesia 2009 103(5):719-725; doi:10.1093/bja/aep237
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© The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Only tetracaine and not other local anaesthetics induce apoptosis in rat cortical astrocytes

W. Y. Lee1,{dagger}, C. J. Park2,{dagger}, T. J. Shin1,{dagger}, K. W. Yum1, T. G. Yoon3, K. S. Seo1 and H. J. Kim1,*

1 Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea
2 Department of Dentistry, Division of Oral and Maxillofacial Surgery, College of Medicine, Hanyang University, Seoul, Republic of Korea
3 Department of Anesthesiology and Pain Medicine, School of Medicine, Konkuk University, Seoul, Republic of Korea

* Corresponding author. E-mail: dentane{at}snu.ac.kr

Background: The potential risks of neurotoxicity due to local anaesthetics after regional anaesthesia have been suggested recently. To evaluate the neurotoxicity of commonly used local anaesthetics, primary cultured rat cortical astrocytes were treated with lidocaine, ropivacaine, bupivacaine, levobupivacaine, and tetracaine.

Methods: Cell death after local anaesthetic treatment was evaluated with a lactate dehydrogenase (LDH) assay. To examine the mechanisms of cell death, reactive oxygen species (ROS) measurement and western blots of poly-ADP ribose polymerase (PARP), procaspase-3, and mitogen-activated protein kinases family members were performed.

Results: Of the local anaesthetics, which were applied at <1 mM for 18 h, only tetracaine significantly increased LDH leakage (P<0.05) and cell death in a dose- and time-dependent manner. Hoechst 33258–propidium iodide staining and western blots with PARP and procaspase-3 antibodies suggested that tetracaine induced apoptosis. ROS levels increased 2-fold at 30 min after tetracaine treatment compared with the control and then decreased. The antioxidants, N-acetylcysteine and trolox, markedly inhibited tetracaine-induced apoptosis.

Conclusions: Tetracaine induced apoptosis through ROS generation. Further studies focusing on the neurotoxicity of tetracaine are needed.

Keywords: anaesthetics local, tetracaine; complications, neurological; toxicity, local anaesthetics


{dagger} W.Y.L. and C.J.P. contributed equally to this study.


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