Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Non-Ionic Surfactants Antagonize Toxicity of Potential Phenolic Endocrine-Disrupting Chemicals, Including Triclosan in Caenorhabditis elegans

  • Alfhili, Mohammad A. (Department of Medicine (Hematology/Oncology Division), Brody School of Medicine at East Carolina University) ;
  • Yoon, Dong Suk (Department of Medicine (Hematology/Oncology Division), Brody School of Medicine at East Carolina University) ;
  • Faten, Taki A. (Department of Biology, East Carolina University) ;
  • Francis, Jocelyn A. (Department of Chemistry, East Carolina University) ;
  • Cha, Dong Seok (Department of Oriental Pharmacy, College of Pharmacy, Woosuk University) ;
  • Zhang, Baohong (Department of Biology, East Carolina University) ;
  • Pan, Xiaoping (Department of Biology, East Carolina University) ;
  • Lee, Myon-Hee (Department of Medicine (Hematology/Oncology Division), Brody School of Medicine at East Carolina University)
  • Received : 2018.09.14
  • Accepted : 2018.10.11
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.

Keywords

E1BJB7_2018_v41n12_1052_f0001.png 이미지

Fig. 1. TCS induces mortality of wildtype worms.

E1BJB7_2018_v41n12_1052_f0002.png 이미지

Fig. 2. Protective role of NISs against TCS.

E1BJB7_2018_v41n12_1052_f0003.png 이미지

Fig. 3. NISs suppress the mortality induced by other phenolic EDCs.

E1BJB7_2018_v41n12_1052_f0004.png 이미지

Fig. 4. Tw20 inhibits TCS-induced mortality via micelle formation.

E1BJB7_2018_v41n12_1052_f0005.png 이미지

Fig. 5. A working model for NIS amelioration of EDC-induced mortality.

References

  1. Allawala, N.A., and Riegelman, S. (1953). The release of antimicrobial agents from solutions of surface-active agents. J. Am. Pharm. Assoc. Am. Pharm. Assoc. 42, 267-275. https://doi.org/10.1002/jps.3030420502
  2. Azzouz, A., Rascon, A.J., and Ballesteros, E. (2016). Simultaneous determination of parabens, alkylphenols, phenylphenols, bisphenol A and triclosan in human urine, blood and breast milk by continuous solid-phase extraction and gas chromatography-mass spectrometry. J. Pharm. Biomed. Anal. 119, 16-26. https://doi.org/10.1016/j.jpba.2015.11.024
  3. Babich, H., and Babich, J.P. (1997). Sodium lauryl sulfate and triclosan: in vitro cytotoxicity studies with gingival cells. Toxicol. Lett. 91, 189-196. https://doi.org/10.1016/S0378-4274(97)00022-2
  4. Benotti, M.J., Trenholm, R.A., Vanderford, B.J., Holady, J.C., Stanford, B.D., and Snyder, S.A. (2009). Pharmaceuticals and endocrine disrupting compounds in U.S. drinking water. Environ. Sci. Technol. 43, 597-603. https://doi.org/10.1021/es801845a
  5. Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
  6. Byford, J.R., Shaw, L.E., Drew, M.G., Pope, G.S., Sauer, M.J., and Darbre, P.D. (2002). Oestrogenic activity of parabens in MCF7 human breast cancer cells. J. Steroid Biochem. Mol. Biol. 80, 49-60. https://doi.org/10.1016/S0960-0760(01)00174-1
  7. Dann, A.B., and Hontela, A. (2011). Triclosan: environmental exposure, toxicity and mechanisms of action. J. Appl. Toxicol. 31, 285-311. https://doi.org/10.1002/jat.1660
  8. Das, G.C., Bacsi, A., Shrivastav, M., Hazra, T.K., and Boldogh, I. (2006). Enhanced gamma-glutamylcysteine synthetase activity decreases drug-induced oxidative stress levels and cytotoxicity. Mol. Carcinog. 45, 635-647. https://doi.org/10.1002/mc.20184
  9. Davies, A.G., Bettinger, J.C., Thiele, T.R., Judy, M.E., and McIntire, S.L. (2004). Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans. Neuron 42, 731-743. https://doi.org/10.1016/j.neuron.2004.05.004
  10. Diamanti-Kandarakis, E., Bourguignon, J.P., Giudice, L.C., Hauser, R., Prins, G.S., Soto, A.M., Zoeller, R.T., and Gore, A.C. (2009). Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 30, 293-342. https://doi.org/10.1210/er.2009-0002
  11. Dong, S., Terasaka, S., and Kiyama, R. (2011). Bisphenol A induces a rapid activation of Erk1/2 through GPR30 in human breast cancer cells. Environ. Pollut. 159, 212-218. https://doi.org/10.1016/j.envpol.2010.09.004
  12. Escalada, M.G., Harwood, J.L., Maillard, J.Y., and Ochs, D. (2005). Triclosan inhibition of fatty acid synthesis and its effect on growth of Escherichia coli and Pseudomonas aeruginosa. J. Antimicrob. Chemother. 55, 879-882. https://doi.org/10.1093/jac/dki123
  13. Fang, J.L., Stingley, R.L., Beland, F.A., Harrouk, W., Lumpkins, D.L., and Howard, P. (2010). Occurrence, efficacy, metabolism, and toxicity of triclosan. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 28, 147-171. https://doi.org/10.1080/10590501.2010.504978
  14. Garcia-Espineira, M.C., Tejeda-Benitez, L.P., and Olivero-Verbel, J. (2018). Toxic effects of bisphenol a, propyl paraben, and triclosan on Caenorhabditis elegans. Int. J. Environ. Res. Public Health 15, pii: E684.
  15. Honnen, S. (2017). Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine. Arch. Toxicol. 91, 2029-2044. https://doi.org/10.1007/s00204-017-1944-7
  16. Hunt, P.R. (2017). The C. elegans model in toxicity testing. J. Appl. Toxicol. 37, 50-59. https://doi.org/10.1002/jat.3357
  17. Ishikawa, T., Zhu, B.L., and Maeda, H. (2006). Effect of sodium azide on the metabolic activity of cultured fetal cells. Toxicol. Ind. Health 22, 337-341. https://doi.org/10.1177/0748233706071737
  18. Kabir, E.R., Rahman, M.S., and Rahman, I. (2015). A review on endocrine disruptors and their possible impacts on human health. Environ. Toxicol. Pharmacol. 40, 241-258. https://doi.org/10.1016/j.etap.2015.06.009
  19. Lenz, K.A., Pattison, C., and Ma, H. (2017). Triclosan (TCS) and triclocarban (TCC) induce systemic toxic effects in a model organism the nematode Caenorhabditis elegans. Environ. Pollut. 231, 462-470. https://doi.org/10.1016/j.envpol.2017.08.036
  20. Li, X., Ying, G.G., Su, H.C., Yang, X.B., and Wang, L. (2010). Simultaneous determination and assessment of 4-nonylphenol, bisphenol A and triclosan in tap water, bottled water and baby bottles. Environ. Int. 36, 557-562. https://doi.org/10.1016/j.envint.2010.04.009
  21. Lu, Y., and Park, K. (2013). Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int. J. Pharm. 453, 198-214. https://doi.org/10.1016/j.ijpharm.2012.08.042
  22. Markovic-Housley, Z., and Garavito, R.M. (1986). Effect of temperature and low pH on structure and stability of matrix porin in micellar detergent solutions. Biochim. Biophys. Acta. 869, 158-170. https://doi.org/10.1016/0167-4838(86)90290-6
  23. McAvoy, D.C., Schatowitz, B., Jacob, M., Hauk, A., and Eckhoff, W.S. (2002). Measurement of triclosan in wastewater treatment systems. Environ. Toxicol. Chem. 21, 1323-1329. https://doi.org/10.1002/etc.5620210701
  24. Meeker, J.D., Yang, T., Ye, X., Calafat, A.M., and Hauser, R. (2011). Urinary concentrations of parabens and serum hormone levels, semen quality parameters, and sperm DNA damage. Environ. Health Perspect. 119, 252-257. https://doi.org/10.1289/ehp.1002238
  25. Miao, M., Yuan, W., Yang, F., Liang, H., Zhou, Z., Li, R., Gao, E., and Li, D.K. (2015). Associations between bisphenol A exposure and reproductive hormones among female workers. Int. J. Environ. Res. Public Health 12, 13240-13250. https://doi.org/10.3390/ijerph121013240
  26. Mitchell, A.G. (1964). Bactericidal activity of chloroxylenol in aqueous solutions of cetomacrogol. J. Pharm. Pharmacol. 16, 533-537. https://doi.org/10.1111/j.2042-7158.1964.tb07509.x
  27. Morvan, C., Halpern, D., Kenanian, G., Hays, C., Anba-Mondoloni, J., Brinster, S., Kennedy, S., Trieu-Cuot, P., Poyart, C., Lamberet, G., et al. (2016). Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials. Nat. Commun. 7, 12944. https://doi.org/10.1038/ncomms12944
  28. Nielsen, C.K., Kjems, J., Mygind, T., Snabe, T., and Meyer, R.L. (2016). Effects of tween 80 on growth and biofilm formation in laboratory media. Front. Microbiol. 7, 1878.
  29. Ogata, N., and Shibata, T. (2000). Binding of alkyl- and alkoxysubstituted simple phenolic compounds to human serum proteins. Res. Commun. Mol. Pathol. Pharmacol. 107, 167-173.
  30. Petersen, R.C. (2016). Triclosan antimicrobial polymers. AIMS. Mol. Sci. 3, 88-103. https://doi.org/10.3934/molsci.2016.1.88
  31. Pupo, M., Pisano, A., Lappano, R., Santolla, M.F., De Francesco, E.M., Abonante, S., Rosano, C., and Maggiolini, M. (2012). Bisphenol A induces gene expression changes and proliferative effects through GPER in breast cancer cells and cancer-associated fibroblasts. Environ. Health Perspect. 120, 1177-1182. https://doi.org/10.1289/ehp.1104526
  32. Rodricks, J.V., Swenberg, J.A., Borzelleca, J.F., Maronpot, R.R., and Shipp, A.M. (2010). Triclosan: a critical review of the experimental data and development of margins of safety for consumer products. Crit. Rev. Toxicol. 40, 422-484. https://doi.org/10.3109/10408441003667514
  33. Schug, T.T., Janesick, A., Blumberg, B., and Heindel, J.J. (2011). Endocrine disrupting chemicals and disease susceptibility. J. Steroid Biochem. Mol. Biol. 127, 204-215. https://doi.org/10.1016/j.jsbmb.2011.08.007
  34. Schwameis, R., Erdogan-Yildirim, Z., Manafi, M., Zeitlinger, M.A., Strommer, S., and Sauermann, R. (2013). Effect of pulmonary surfactant on antimicrobial activity in vitro. Antimicrob. Agents Chemother. 57, 5151-5154. https://doi.org/10.1128/AAC.00778-13
  35. Sengupta, N., Litoff, E.J., and Baldwin, W.S. (2015). The HR96 activator, atrazine, reduces sensitivity of D. magna to triclosan and DHA. Chemosphere 128, 299-306. https://doi.org/10.1016/j.chemosphere.2015.02.027
  36. Song, B.M., and Avery, L. (2013). The pharynx of the nematode C. elegans: A model system for the study of motor control. Worm 2, e21833. https://doi.org/10.4161/worm.21833
  37. Swedenborg, E., Ruegg, J., Makela, S., and Pongratz, I. (2009). Endocrine disruptive chemicals: mechanisms of action and involvement in metabolic disorders. J. Mol. Endocrinol. 43, 1-10. https://doi.org/10.1677/JME-08-0132
  38. Taylor, T.J., Seitz, E.P., Fox, P., Fischler, G.E., Fuls, J.L., and Weidner, P.L. (2004). Physicochemical factors affecting the rapid bactericidal efficacy of the phenolic antibacterial triclosan. Int. J. Cosmet. Sci. 26, 111-116. https://doi.org/10.1111/j.1467-2494.2004.00205.x
  39. Tejeda-Benitez, L., and Olivero-Verbel, J. (2016). Caenorhabditis elegans, a biological model for research in toxicology. Rev. Environ. Contam. Toxicol. 237, 1-35.
  40. Toutain-Kidd, C.M., Kadivar, S.C., Bramante, C.T., Bobin, S.A., and Zegans, M.E. (2009). Polysorbate 80 inhibition of Pseudomonas aeruginosa biofilm formation and its cleavage by the secreted lipase LipA. Antimicrob. Agents Chemother. 53, 136-145. https://doi.org/10.1128/AAC.00500-08
  41. Vingskes, A.K., and Spann, N. (2018). The toxicity of a mixture of two antiseptics, triclosan and triclocarban, on reproduction and growth of the nematode Caenorhabditis elegans. Ecotoxicology 27, 420-429. https://doi.org/10.1007/s10646-018-1905-9
  42. Watanabe, M., Mitani, N., Ishii, N., and Miki, K. (2005). A mutation in a cuticle collagen causes hypersensitivity to the endocrine disrupting chemical, bisphenol A, in Caenorhabditis elegans. Mutat. Res. 570, 71-80. https://doi.org/10.1016/j.mrfmmm.2004.10.005
  43. Weatherly, L.M., Shim, J., Hashmi, H.N., Kennedy, R.H., Hess, S.T., and Gosse, J.A. (2016). Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes. J. Appl. Toxicol. 36, 777-789. https://doi.org/10.1002/jat.3209
  44. Ye, X., Bishop, A.M., Reidy, J.A., Needham, L.L., and Calafat, A.M. (2006). Parabens as urinary biomarkers of exposure in humans. Environ. Health Perspect. 114, 1843-1846. https://doi.org/10.1289/ehp.9413
  45. Yoon, D.S., Choi, Y., Cha, D.S., Zhang, P., Choi, S.M., Alfhili, M.A., Polli, J.R., Pendergrass, D., Taki, F.A., Kapalavavi, B., et al. (2017). Triclosan disrupts SKN-1/Nrf2-mediated oxidative stress response in C. elegans and human mesenchymal stem cells. Sci. Rep. 7, 12592. https://doi.org/10.1038/s41598-017-12719-3
  46. Yoon, D.S., Pendergrass, D.L., and Lee, M.H. (2016). A simple and rapid method for combining fluorescent in situ RNA hybridization (FISH) and immunofluorescence in the C. elegans germline. MethodsX 3, 378-385. https://doi.org/10.1016/j.mex.2016.05.001

Cited by

  1. Triclosan: An Update on Biochemical and Molecular Mechanisms vol.2019, pp.None, 2018, https://doi.org/10.1155/2019/1607304
  2. Effects of emulsion, dispersion, and blend electrospinning on hyaluronic acid nanofibers with incorporated antiseptics vol.194, pp.None, 2022, https://doi.org/10.1016/j.ijbiomac.2021.11.118