Cultures of rat gingival fibroblasts were exposed to various dilutions of lidocaine hydrochloride (Xylocaine®), mepivacaine hydrochloride (Carbocaine®), and prilocaine hydrochloride (Citanest®). All three anesthetics produced cell-rounding and detachment from the substrate, which varied depending on the anesthetic, its concentration in the medium, and the duration of exposure (p<0.001). Effects were not pH-dependent in the range of 7.0-7.4 and were not modified by epinephrine in the concentration normally present in commercially prepared anesthetic solutions. Prilocaine produced morphological changes at a greater rate and at a lower concentration than did lidocaine or mepivacaine (p<0.001). The effects elicited by prilocaine were irreversible, since prolonged exposures to it resulted in various toxic effects: (1) detachment of the cells from the substrate, and (2) development of pyknotic nuclei and circumferential halos in cells that remained attached. The study strongly suggested that prilocaine has the potential to be more toxic to fibroblasts than either mepivacaine or lidocaine, a situation of potential clinical importance.
Get full access to this article
View all access options for this article.
References
1.
Bateman, P.O. (1974): Multiple Allergy to Local Anaesthetics Including Prilocaine, Med J Aust2: 449-450.
2.
Brunk, V.; Collins, V.P.; and Arro, E. (1980): The Fixation, Dehydration, Drying and Coating of Cultured Cells for SEM, J Microsc123: 121-131.
3.
Byers, M.R.; Hendrickson, A.E.; Fink, B.R.; Kennedy, R.D.; and Middaugh, M.E. (1973): Effects of Lidocaine on Axonal Morphology, Microtubules, and Rapid Transport in Rabbit Vagus Nerve in vitro, J Neurobiol4: 125-143.
4.
Cullen, B.F. and Haschke, R.H. (1974): Local Anesthetic Inhibition of Phagocytosis and Metabolism of Human Leucocytes, Anesthesiol40 : 142-146.
5.
Chvapil, M.; Hameroff, S.R.; O'Dea, K.; and Peacock, E.E. (1979): Local Anesthetics and Wound Healing, J Surg Res27: 367-371.
6.
Edstrom, A.; Erkell, L.J.; and Hansson, H.A. (1975): Reversal of Morphological Differentiation of Mouse Neuroblastoma Cells by Mitosis-inhibitors and Anesthetics, Virchows Arch B Cell Pathol19: 101-113.
7.
Eichhorn, J.H. and Peterkofsky, B. (1979): Local Anesthetic-induced Inhibition of Collagen Secretion in Cultured Cells Under Conditions Where Microtubules Are Not Depolymerized by These Agents, J Cell Biol81: 26-42.
8.
Eyring, H.; Woodbury, J.W.; and D'Arrigo, J.S. (1973): A Molecular Mechanism of General Anesthesia, Anesthesiol38: 415-424.
9.
Fink, B.R.; Kennedy, R.D.; Hendrickson, A.E.; and Middaugh, M.E. (1972): Lidocaine Inhibition of Rapid Axonal Transport , Anesthesiol36: 422-432.
10.
Gail, M.H. and Boone, C.W. (1972): Prilocaine Inhibition of Fibroblast Motility and Proliferation, Exp Cell Res73: 252-255.
11.
Giddon, D.B. and Lindhe, J. (1972): In vivo Quantitation of Local Anesthetic Suppression of Leucocyte Adherence, Am J Pathol68: 327-338.
12.
Goransson, K. (1976): Hypersensitivity to Prilocaine, Dermatologia152: 158-160.
13.
Hagiwara, Y.; Atsumi, S.; and Ozawa, E. (1985): Reversible Suppression of Growth and Differentiation of Cultured Chick Myogenic Cells with Very Low Concentrations of Dibucaine , J Pharmacobiol-Dyn8: 311-319.
14.
Hagiwara, Y. and Ozawa, E. (1985): Toxicity of Local Anaesthetics on Myogenic Cells in Culture, J Pharmacobiol-Dyn8: 106-113.
15.
Haschke, R.H.; Byers, M.R.; and Fink, B.R. (1974): Effects of Lidocaine on Rabbit Brain Microtubular Protein, J Neurochem22: 837-843.
16.
Hoidal, J.R.; White, J.G.; and Repine, J.E. (1979): Influence of Cationic Local Anesthetics on the Metabolism and Ultrastructure of Human Alveolar Macrophages, J Lab Clin Med93: 857-866.
17.
Jackson, S.H. (1971): The Metabolic Effects of Nonvolatile Anesthetics on Mammalian Hepatoma Cells in vitro. II. Inhibition of Macromolecular Precursor Incorporation, Anesthesiol35: 268-273.
18.
Jackson, S.H. and Epstein, R.A. (1971): The Metabolic Effects of Nonvolatile Anesthetics on Mammalian Hepatoma Cells in vitro. I. Inhibition of Cell Replication, Anesthesiol34: 409-414.
19.
Kasten, F.H.; Felder, S.M.; Gettleman, L.; and Alche-Diak, T. (1982): A Model Culture System with Human Gingival Fibroblasts for Evaluating the Cytotoxicity of Dental Materials, In Vitro18: 650-660.
20.
Lever, M.J.; Miller, K.W.; Paton, W.D.M.; and Smith, E.B. (1971): Pressure Reversal of Anaesthesia, Nature231: 368-371.
21.
Marmary, Y.; Brunette, D.M.; and Heersche, J.N.M. (1976): Differences in vitro Between Cells Derived from Periodontal Ligament and Skin of Macaca irus, Arch Oral Biol21: 709-716.
22.
Miller, K. and Foster, J.R. (1981): Evidence of Transient Effect by Lignocaine on Alveolar Macrophage Morphology, J Immunol Meth43: 163-168.
23.
Nicolson, G.L. (1976): Cell Shape Changes and Transmembrane Receptor Uncoupling Induced by Tertiary Amine Local Anesthetics, J Supramolec Struct5: 65-72.
24.
Nicolson, G.L.; Smith, J.R.; and Poste, G. (1976): Effects of Local Anesthetics on Cell Morphology and Membrane-associated Cytoskeletal Organization in BALB/3T3 Cells, J Cell Biol68: 395-402.
25.
Papahadjopoulos, D. (1972): Studies on the Mechanism of Action of Local Anesthetics With Phospholipid Model Membranes, Biochim Biophys Acta265: 169-186.
26.
Papahadjopoulos, D.; Jacobson, K.; Poste, G.; and Shepard, G. (1975): Effects of Local Anesthetics on Membrane Properties. I. Changes in the Fluidity of Phospholipid Bilayers, Biochim Biophys Acta394: 504-519.
27.
Poste, G. and Allison, A.C. (1973): Membrane Fusion, Biochim Biophys Acta300: 421-465.
28.
Rabinovitch, M. and Destefano, M.J. (1974): Macrophage Spreading in vitro. III. The Effect of Metabolic Inhibitors, Anesthetics and Other Drugs on Spreading Induced by Subtilisin, Exp Cell Res88: 153-162.
29.
Rabinovitch, M. and Destefano, M.J. (1975): Cell to Substrate Adhesion and Spreading: Inhibition by Cationic Anesthetics, J Cell Physiol85: 189-194.
30.
Rabinovitch, M. and Destefano, M.J. (1976): Cell Shape Changes Induced by Cationic Anesthetics , J Exp Med143: 290-304.
31.
Ritchie, J.M. and Greengard, P. (1966): On the Mode of Action of Local Anesthetics, Ann Rev Pharmacol6: 405-430.
32.
Roth, S. and Seeman, P. (1971): All Lipid-soluble Anaesthetics Protect Red Cells , Nat New Biol231: 284-285.
33.
Ryan, G.B.; Unanue, E.R.; and Karnovsky, M.J. (1974): Inhibition of Surface Capping of Macromolecules by Local Anesthetics and Tranquillisers, Nature250: 56-57.
34.
Spangberg, L. and Isaksson, B. (1970): Cytotoxic Effect of Carbocain and Marcain, Acta Odontol Scand28: 417-424.
35.
Sturrock, J.E. and Nunn, J.F. (1979): Cytotoxic Effects of Procaine, Lignocaine and Bupivacaine, Br J Anaesth51: 273-281.
36.
Yang, W.C.T.; Strasser, F.F.; and Pomerat, C.M. (1965): Mechanism of Drug-induced Vacuolization in Tissue Culture, Exp Cell Res38: 495-506.
37.
Yeoman, C.M. (1982): Hypersensitivity to Prilocaine, Br Dent J153: 69.
