Citotoxicidad y genotoxicidad del clorhidrato de octenidina sobre células humanas

Carlos Galván-Caudillo, René Hernández-Delgadillo, Gustavo Martínez-González, Claudio Cabral-Romero


El clorhidrato de  octenidina se emplea como ingrediente principal de enjuagues bucales debido a sus  propiedades bactericidas y antibiopelícula. Aunque la octenidina es ampliamente utilizada, no hay reportes previos que indiquen su posible efecto tóxico en los seres humanos. El objetivo de esta investigación fue analizar la citotoxicidad de la octenidina en las células epiteliales humanas (HeLa). Células HeLa fueron cultivadas y expuestas a varias concentraciones de octenidina y la viabilidad celular se midió mediante ensayos de MTT. Los resultados obtenidos mostraron que no había células vivas después de 24 hrs de incubación al ser tratadas con 0,0125 a 0,05% de octenidina. Sorprendentemente,  las mismas concentraciones de octenidina tuvieron un efecto citotóxico en todas las células HeLa después de sólo 5 minutos de exposición. Estos datos fueron apoyados por la observación de las mismas cultivadas con octenidina mediante microscopía de fluorescencia, que indicaron el daño sobre la membrana plasmática, probablemente alterando su permeabilidad. Empleando ensayos de genotoxicidad, se encontró que la octenidina causa lesiones al ADN genómico. Las concentraciones más bajas de octenidina indujeron un aumento de los niveles de IL-6. Sin embargo, no promueve la apoptosis entre las células epiteliales. Como conclusión; la octenidina es altamente tóxico en las células humanas, por lo tanto los efectos benéficos y nocivos de la octenidina en los seres humanos deben ser valorados en estudios in vivo.

Palabras clave


Texto completo:



Van Strydonck, D. A., Slot, D. E., Van der Velden, U. & Van der Weijden, F. Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. Journal of clinical periodontology 39, 1042-1055, doi:10.1111/j.1600-051X.2012.01883.x (2012).

Chainani, S. H. et al. Antiplaque and antigingivitis efficacy of triphala and chlorhexidine mouthrinse among schoolchildren - a cross-over, double-blind, randomised controlled trial. Oral health & preventive dentistry 12, 209-217, doi:10.3290/j.ohpd.a32674 (2014).

Schroeder, H. E. Formation and inhibition of dental calculus. Journal of periodontology 40, 643-646, doi:10.1902/jop.1969.40.11.643 (1969).

Jones, C. G. Chlorhexidine: is it still the gold standard? Periodontology 2000 15, 55-62 (1997).

Louis, S. M. & Pearson, R. M. A comparison of the effects of nonoxynol-9 and chlorhexidine on sperm motility. Contraception 32, 199-205 (1985).

Kenney, E. B., Saxe, S. R. & Bowles, R. D. Effect of chlorhexidine on human polymorphonuclear leucocytes. Archives of oral biology 17, 1633-1636 (1972).

Knuuttila, M. & Soderling, E. Effect of chlorhexidine on the release of lysosomal enzymes from cultured macrophages. Acta odontologica Scandinavica 39, 285-289 (1981).

Helgeland, K., Heyden, G. & Rolla, G. Effect of chlorhexidine on animal cells in vitro. Scandinavian journal of dental research 79, 209-215 (1971).

Pucher, J. J. & Daniel, J. C. The effects of chlorhexidine digluconate on human fibroblasts in vitro. Journal of periodontology 63, 526-532, doi:10.1902/jop.1992.63.6.526 (1992).

Patters, M. R. et al. Inhibition of plaque formation in humans by octenidine mouthrinse. Journal of periodontal research 18, 212-219 (1983).

Shern, R. J., Monell-Torrens, E. & Kingman, A. Effect of two recently developed antiseptics on dental plaque and caries in rats. Caries research 19, 458-465 (1985).

Decker, E. M., Weiger, R., Wiech, I., Heide, P. E. & Brecx, M. Comparison of antiadhesive and antibacterial effects of antiseptics on Streptococcus sanguinis. European journal of oral sciences 111, 144-148 (2003).

Tandjung, L. et al. Octenidine in root canal and dentine disinfection ex vivo. International endodontic journal 40, 845-851, doi:10.1111/j.1365-2591.2007.01279.x (2007).

Youngner, J. S. Monolayer tissue cultures. I. Preparation and standardization of suspensions of trypsin-dispersed monkey kidney cells. Proc Soc Exp Biol Med 85, 202-205 (1954).

Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods 65, 55-63 (1983).

Liu, Y., Peterson, D. A., Kimura, H. & Schubert, D. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Journal of neurochemistry 69, 581-593 (1997).

Bozyczko-Coyne, D., McKenna, B. W., Connors, T. J. & Neff, N. T. A rapid fluorometric assay to measure neuronal survival in vitro. Journal of neuroscience methods 50, 205-216 (1993).

Akeson, A. L. & Woods, C. W. A fluorometric assay for the quantitation of cell adherence to endothelial cells. Journal of immunological methods 163, 181-185 (1993).

Kubista, M., Akerman, B. & Norden, B. Characterization of interaction between DNA and 4',6-diamidino-2-phenylindole by optical spectroscopy. Biochemistry 26, 4545-4553 (1987).

Ostling, O. & Johanson, K. J. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochemical and biophysical research communications 123, 291-298 (1984).

De Boeck, M., Touil, N., De Visscher, G., Vande, P. A. & Kirsch-Volders, M. Validation and implementation of an internal standard in comet assay analysis. Mutation research 469, 181-197 (2000).

Soda, K., Kano, Y., Kawakami, M. & Konishi, F. Excessive increase of serum interleukin 6 jeopardizes host defense against multi-bacterial infection. Cytokine 21, 295-302 (2003).

Chung, Y. C. & Chang, Y. F. Serum interleukin-6 levels reflect the disease status of colorectal cancer. Journal of surgical oncology 83, 222-226, doi:10.1002/jso.10269 (2003).

Boersma, A. W., Nooter, K., Oostrum, R. G. & Stoter, G. Quantification of apoptotic cells with fluorescein isothiocyanate-labeled annexin V in chinese hamster ovary cell cultures treated with cisplatin. Cytometry 24, 123-130, doi:10.1002/(SICI)1097-0320(19960601)24:2<123::AID-CYTO4>3.0.CO;2-K (1996).

Zelenin, A. V. et al. 7-Amino-actinomycin D as a specific fluorophore for DNA content analysis by laser flow cytometry. Cytometry 5, 348-354, doi:10.1002/cyto.990050410 (1984).

Costerton, J. W. Overview of microbial biofilms. Journal of industrial microbiology 15, 137-140 (1995).

Loe, H., Anerud, A., Boysen, H. & Smith, M. The natural history of periodontal disease in man. Study design and baseline data. Journal of periodontal research 13, 550-562 (1978).

Loe, H., Theilade, E. & Jensen, S. B. Experimental Gingivitis in Man. Journal of periodontology 36, 177-187, doi:10.1902/jop.1965.36.3.177 (1965).

Hossainian, N., Slot, D. E., Afennich, F. & Van der Weijden, G. A. The effects of hydrogen peroxide mouthwashes on the prevention of plaque and gingival inflammation: a systematic review. International journal of dental hygiene 9, 171-181, doi:10.1111/j.1601-5037.2010.00492.x (2011).

Afennich, F., Slot, D. E., Hossainian, N. & Van der Weijden, G. A. The effect of hexetidine mouthwash on the prevention of plaque and gingival inflammation: a systematic review. International journal of dental hygiene 9, 182-190, doi:10.1111/j.1601-5037.2010.00478.x (2011).

Haps, S., Slot, D. E., Berchier, C. E. & Van der Weijden, G. A. The effect of cetylpyridinium chloride-containing mouth rinses as adjuncts to toothbrushing on plaque and parameters of gingival inflammation: a systematic review. International journal of dental hygiene 6, 290-303, doi:10.1111/j.1601-5037.2008.00344.x (2008).

Berchier, C. E., Slot, D. E., Haps, S. & Van der Weijden, G. A. The efficacy of dental floss in addition to a toothbrush on plaque and parameters of gingival inflammation: a systematic review. International journal of dental hygiene 6, 265-279, doi:10.1111/j.1601-5037.2008.00336.x (2008).

Silvestri, D. L. & McEnery-Stonelake, M. Chlorhexidine: uses and adverse reactions. Dermatitis : contact, atopic, occupational, drug 24, 112-118, doi:10.1097/DER.0b013e3182905561 (2013).

Bailey, D. M. et al. Bispyridinamines: a new class of topical antimicrobial agents as inhibitors of dental plaque. Journal of medicinal chemistry 27, 1457-1464 (1984).

Emilson, C. G., Bowen, W. H., Robrish, S. A. & Kemp, C. W. Effect of the antibacterial agents octenidine and chlorhexidine on the plaque flora in primates. Scandinavian journal of dental research 89, 384-392 (1981).

Beiswanger, B. B., Mallatt, M. E., Mau, M. S., Jackson, R. D. & Hennon, D. K. The clinical effects of a mouthrinse containing 0.1% octenidine. Journal of dental research 69, 454-457 (1990).

Kocak, M. M., Ozcan, S., Kocak, S., Topuz, O. & Erten, H. Comparison of the efficacy of three different mouthrinse solutions in decreasing the level of streptococcus mutans in saliva. European journal of dentistry 3, 57-61 (2009).

Mariotti, A. J. & Rumpf, D. A. Chlorhexidine-induced changes to human gingival fibroblast collagen and non-collagen protein production. Journal of periodontology 70, 1443-1448, doi:10.1902/jop.1999.70.12.1443 (1999).

Rushton, A. Safety of Hibitane. II. Human experience. Journal of clinical periodontology 4, 73-79 (1977).

Haanen, C. & Vermes, I. Apoptosis and inflammation. Mediators of inflammation 4, 5-15, doi:10.1155/S0962935195000020 (1995).

ISSN: 2007-9052

Indexada en Latindex.

Indexada en Google académico.

Indexada en INFOMED - Cuba.

Indexada en REDIB - España.


Contador y estadísticas gratis para su sitio web en