Browse > Article
http://dx.doi.org/10.14348/molcells.2018.0378

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)
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
Caenorhabditis elegans; endocrine-disrupting chemicals; micelle; non-ionic surfactants; phenolic compound; PMP-3/ABC transporter; triclosan;
Citations & Related Records
연도 인용수 순위
  • Reference
1 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.
2 Petersen, R.C. (2016). Triclosan antimicrobial polymers. AIMS. Mol. Sci. 3, 88-103.   DOI
3 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.   DOI
4 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.   DOI
5 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.   DOI
6 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.   DOI
7 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.   DOI
8 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.   DOI
9 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.   DOI
10 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.   DOI
11 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.   DOI
12 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.   DOI
13 Tejeda-Benitez, L., and Olivero-Verbel, J. (2016). Caenorhabditis elegans, a biological model for research in toxicology. Rev. Environ. Contam. Toxicol. 237, 1-35.
14 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.   DOI
15 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.   DOI
16 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.   DOI
17 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.   DOI
18 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.   DOI
19 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.   DOI
20 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.   DOI
21 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.   DOI
22 Babich, H., and Babich, J.P. (1997). Sodium lauryl sulfate and triclosan: in vitro cytotoxicity studies with gingival cells. Toxicol. Lett. 91, 189-196.   DOI
23 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.   DOI
24 Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
25 Dann, A.B., and Hontela, A. (2011). Triclosan: environmental exposure, toxicity and mechanisms of action. J. Appl. Toxicol. 31, 285-311.   DOI
26 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.   DOI
27 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.   DOI
28 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.   DOI
29 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.   DOI
30 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.   DOI
31 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.   DOI
32 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.
33 Honnen, S. (2017). Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine. Arch. Toxicol. 91, 2029-2044.   DOI
34 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.   DOI
35 Hunt, P.R. (2017). The C. elegans model in toxicity testing. J. Appl. Toxicol. 37, 50-59.   DOI
36 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.   DOI
37 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.   DOI
38 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.   DOI
39 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.   DOI
40 Lu, Y., and Park, K. (2013). Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int. J. Pharm. 453, 198-214.   DOI
41 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.   DOI
42 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.   DOI
43 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.   DOI
44 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.   DOI
45 Mitchell, A.G. (1964). Bactericidal activity of chloroxylenol in aqueous solutions of cetomacrogol. J. Pharm. Pharmacol. 16, 533-537.   DOI
46 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.