International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Cytotoxicity of Bupivacaine in Odontoblasts

  • Kim, Hyun-Jeong (Department of Dental Anesthesiology and Dental Research Institute, Seoul National University School of Dentistry)
  • Published : 2007.06.30
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Abstract

In this study, the cytotoxicity of commonly used local anesthetics was evaluated on odontoblasts which are essential for pulpal homeostasis in vitro. Local anesthetics, such as articaine, bupivacaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, and procaine, were tested on the odontoblast cell line, MDPC-23. The concentration-and time-dependent cytotoxic effects of local anesthetics on odontoblasts were measured by MTT assay. Among local anesthetics treated for 18 h, only bupivacaine significantly showed cell death in a concentration-($LC_{50}=1.2mM$) and time-dependent manner. To confirm cell death induced by bupivacaine, the observation of cell morphology and FACS using Annexin V and propidium iodide (PI) staining were performed. As a result of Annexin V and PI staining, as well as the morphological change, only bupivacaine induced apoptotic cell death on odontoblasts when compared with levobupivacaine and lidocaine. These results suggest that bupivacaine might affect normal pulpal integrity even after uneventful local anesthesia.

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References

  1. Botero, T. M., Mantellini, M. G., Song, W., Hanks, C. T., and Nor, J. E.: Effect of lipopolysaccharides on vascular endothelial growth factor expression in mouse pulp cells and macrophages. Eur J Oral Sci. 111:228-34, 2003 https://doi.org/10.1034/j.1600-0722.2003.00041.x
  2. Costa, C. A., Edwards, C. A., and Hanks, C. T.: Cytotoxic effects of cleansing solutions recommended for chemical lavage of pulp exposures. Am J Dent. 14:25-30, 2001
  3. van Engeland M, Nieland, L. J., Ramaekers, F. C., Schutte, B., Reutelingsperger, C. P.: Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 31:1-9, 1998 https://doi.org/10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R
  4. Friederich, P. and Schmitz, T. P.: Lidocaine-induced cell death in a human model of neuronal apoptosis. Eur J Anaesthesiol. 19:564-70, 2002 https://doi.org/10.1017/S0265021502000911
  5. Haas, D. A.: Localized complications from local anesthesia. J Calif Dent Assoc. 26:677-82, 1998
  6. Hall, P. A.: Assessing apoptosis: a critical survey. Endocr Relat Cancer. 6:3-8, 1999 https://doi.org/10.1677/erc.0.0060003
  7. Hanks, C. T., Sun, Z. L., Fang, D. N., Edwards, C. A., Wataha, J. C., Ritchie, H. H., et al.: Cloned 3T6 cell line from CD-1 mouse fetal molar dental papillae. Connect Tissue Res. 37:233-49, 1998 https://doi.org/10.3109/03008209809002442
  8. Hargreaves, K. M. and Keiser, K.: New advances in the management of endodontic pain emergencies. J Calif Dent Assoc. 32:469-73, 2004
  9. Janke, V., von Neuhoff, N., Schlegelberger, B., Leyhausen, G., and Geurtsen, W.: TEGDMA causes apoptosis in primary human gingival fibroblasts. J Dent Res. 82:814-8, 2003 https://doi.org/10.1177/154405910308201010
  10. Johnson, R. B. and Dowse, C. M.: Comparative effects of local anesthetic preparations on gingival fibroblasts of the rat. J Dent Res. 65:1125-32, 1986 https://doi.org/10.1177/00220345860650090401
  11. Kasaba, T., Onizuka, S., and Takasaki, M.: Procaine and mepivacaine have less toxicity in vitro than other clinically used local anesthetics. Anesth Analg. 97:85-90, 2003
  12. Kerr, J. F., Wyllie, A. H., and Currie, A. R.: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239-57, 1972 https://doi.org/10.1038/bjc.1972.33
  13. Kohase, H., Miyamoto, T., and Umino, M.: A new method of continuous maxillary nerve block with an indwelling catheter. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 94:162-6, 2002 https://doi.org/10.1067/moe.2002.124857
  14. Komai, H. and Lokuta, A. J.: Interaction of bupivacaine and tetracaine with the sarcoplasmic reticulum Ca2+ release channel of skeletal and cardiac muscles. Anesthesiology. 90:835-43, 1999 https://doi.org/10.1097/00000542-199903000-00027
  15. Kytta, J., Heinonen, E., Rosenberg, P. H., Wahlstrom, T., Gripenberg, J., and Huopaniemi, T.: Effects of repeated bupivacaine administration on sciatic nerve and surrounding muscle tissue in rats. Acta Anaesthesiol Scand. 30:625-9, 1986 https://doi.org/10.1111/j.1399-6576.1986.tb02488.x
  16. Majno, G. and Joris, I.: Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 146:3-15, 1995
  17. Mantellini, M. G., Botero, T. M., Yaman, P., Dennison, J. B., Hanks, C. T., and Nor, J.E.: Adhesive resin induces apoptosis and cell-cycle arrest of pulp cells. J Dent Res. 82:592-6, 2003 https://doi.org/10.1177/154405910308200804
  18. Park, C. J., Park, S. A., Yoon, T. G., Lee, S. J., Yum, K. W., and Kim, H. J.: Bupivacaine induces apoptosis via ROS in the Schwann cell line. J Dent Res. 84:852-57, 2005 https://doi.org/10.1177/154405910508400914
  19. de Souza Costa, C. A., Hebling, J., Garcia-Godoy, F., and Hanks, C. T.: In vitro cytotoxicity of five glass-ionomer cements. Biomaterials. 24:3853-8, 2003 https://doi.org/10.1016/S0142-9612(03)00253-9
  20. Sun, Z. L., Fang, D. N., Wu, X. Y., Ritchie, H. H., Begue-Kirn, C., Wataha, J. C., et al.: Expression of dentin sialoprotein (DSP) and other molecular determinants by a new cell line from dental papillae, MDPC-23. Connect Tissue Res. 37:251-61, 1998 https://doi.org/10.3109/03008209809002443
  21. Tan, Z., Dohi, S., Chen, J., Banno, Y., and Nozawa, Y.: Involvement of the mitogen-activated protein kinase family in tetracaine-induced PC12 cell death. Anesthesiology. 96:1191-201, 2002 https://doi.org/10.1097/00000542-200205000-00024
  22. Telles, P. D. and Hanks, C. T., Machado, M. A., and Nor. J. E.: Lipoteichoic acid up-regulates VEGF expression in macrophages and pulp cells. J Dent Res. 82:466-70, 2003 https://doi.org/10.1177/154405910308200612
  23. Torabinejad, M., Peters, D. L., Peckham, N., Rentchler, L. R., and Richardson, J.: Electron microscopic changes in human pulps after intraligamental injection. Oral Surg Oral Med Oral Pathol. 76:219-24, 1993 https://doi.org/10.1016/0030-4220(93)90208-L
  24. Zink, W., Seif, C., Bohl, J.R., Hacke, N., Braun, P. M., Sinner, B., et al.: The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades. Anesth Analg. 97:1173-9, 2003