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http://dx.doi.org/10.4062/biomolther.2015.164

Effects of Triclosan on Neural Stem Cell Viability and Survival  

Park, Bo Kyung (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
Gonzales, Edson Luck T. (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
Yang, Sung Min (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
Bang, Minji (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
Choi, Chang Soon (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
Shin, Chan Young (Department of Neuroscience, School of Medicine, and Neuroscience Research Center, SMART-IABS and KU Open Innovation Center, Konkuk University)
Publication Information
Biomolecules & Therapeutics / v.24, no.1, 2016 , pp. 99-107 More about this Journal
Abstract
Triclosan is an antimicrobial or sanitizing agent used in personal care and household products such as toothpaste, soaps, mouthwashes and kitchen utensils. There are increasing evidence of the potentially harmful effects of triclosan in many systemic and cellular processes of the body. In this study, we investigated the effects of triclosan in the survivability of cultured rat neural stem cells (NSCs). Cortical cells from embryonic day 14 rat embryos were isolated and cultured in vitro. After stabilizing the culture, triclosan was introduced to the cells with concentrations ranging from $1{\mu}M$ to $50{\mu}M$ and in varied time periods. Thereafter, cell viability parameters were measured using MTT assay and PI staining. TCS decreased the cell viability of treated NSC in a concentration-dependent manner along with increased expressions of apoptotic markers, cleaved caspase-3 and Bax, while reduced expression of Bcl2. To explore the mechanisms underlying the effects of TCS in NSC, we measured the activation of MAPKs and intracellular ROS. TCS at $50{\mu}M$ induced the activations of both p38 and JNK, which may adversely affect cell survival. In contrast, the activities of ERK, Akt and PI3K, which are positively correlated with cell survival, were inhibited. Moreover, TCS at this concentration augmented the ROS generation in treated NSC and depleted the glutathione activity. Taken together, these results suggest that TCS can induce neurodegenerative effects in developing rat brains through mechanisms involving ROS activation and apoptosis initiation.
Keywords
Triclosan; Apoptosis; Oxidation; Rat neural stem cells; MAPK signaling;
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1 Ahn, K. C., Zhao, B., Chen, J., Cherednichenko, G., Sanmarti, E., Denison, M. S., Lasley, B., Pessah, I. N., Kultz, D. and Chang, D. P. (2008) In vitro biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: receptor-based bioassay screens. Environ. Health Perspect. 116, 1203-1210.   DOI
2 Aiello, A. E., Larson, E. L. and Levy, S. B. (2007) Consumer antibacterial soaps: effective or just risky? Clin. Infect. Dis. 45, S137-S147.   DOI
3 Allmyr, M., Adolfsson-Erici, M., McLachlan, M. S. and Sandborgh-Englund, G. (2006) Triclosan in plasma and milk from Swedish nursing mothers and their exposure via personal care products. Sci. Total Environ. 372, 87-93.   DOI
4 Bedoux, G., Roig, B., Thomas, O., Dupont, V. and Le Bot, B. (2012) Occurrence and toxicity of antimicrobial triclosan and by-products in the environment. Environ. Sci. Pollut. Res. 19, 1044-1065.   DOI
5 Brausch, J. M. and Rand, G. M. (2011) A review of personal care products in the aquatic environment: Environmental concentrations and toxicity. Chemosphere 82, 1518-1532.   DOI
6 Brunet, A., Datta, S. R. and Greenberg, M. E. (2001) Transcriptiondependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr. Opin. Neurobiol. 11, 297-305.   DOI
7 Calafat, A. M., Ye, X., Wong, L.-Y., Reidy, J. A. and Needham, L. L. (2008) Urinary concentrations of triclosan in the US population: 2003-2004. Environ. Health Perspect. 116, 303-307.
8 Chen, J., Ahn, K. C., Gee, N. A., Gee, S. J., Hammock, B. D. and Lasley, B. L. (2007) Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicol. Appl. Pharmacol. 221, 278-284.   DOI
9 Chen, X., Xu, B., Han, X., Mao, Z., Chen, M., Du, G., Talbot, P., Wang, X. and Xia, Y. (2015) The effects of triclosan on pluripotency factors and development of mouse embryonic stem cells and zebrafish. Arch. Toxicol. 89, 635-646.   DOI
10 Geens, T., Neels, H. and Covaci, A. (2012) Distribution of bisphenol-A, triclosan and n-nonylphenol in human adipose tissue, liver and brain. Chemosphere 87, 796-802.   DOI
11 Glaser, A. (2004) The ubiquitous triclosan. A common antibacterial agent exposed. Pestic. You 24, 12-17.
12 Ito, K. and Suda, T. (2014) Metabolic requirements for the maintenance of self-renewing stem cells. Nat. Rev. Mol. Cell Biol. 15, 243-256.   DOI
13 Go, H. S., Kim, K. C., Choi, C. S., Jeon, S. J., Kwon, K. J., Han, S.-H., Lee, J., Cheong, J. H., Ryu, J. H., Kim, C.-H., Ko, K. H. and Shin, C. Y. (2012) Prenatal exposure to valproic acid increases the neural progenitor cell pool and induces macrocephaly in rat brain via a mechanism involving the GSK-$3{\beta}$/${\beta}$-catenin pathway. Neuropharmacology 63, 1028-1041.   DOI
14 Ishibashi, H., Matsumura, N., Hirano, M., Matsuoka, M., Shiratsuchi, H., Ishibashi, Y., Takao, Y. and Arizono, K. (2004) Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin. Aquat. Toxicol. 67, 167-179.   DOI
15 Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K. and Ikeda, Y. (2006) Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat. Med. 12, 446-451.   DOI
16 Jacobs, M. N., Nolan, G. T. and Hood, S. R. (2005) Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol. Appl. Pharmacol. 209, 123-133.   DOI
17 Johnson, G. L. and Lapadat, R. (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912.   DOI
18 Kim, K. C., Lee, D. K., Go, H. S., Kim, P., Choi, C. S., Kim, J. W., Jeon, S. J., Song, M.-R. and Shin, C. Y. (2014) Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring. Mol. Neurobiol. 49, 512-528.   DOI
19 Le Belle, J. E., Orozco, N. M., Paucar, A. A., Saxe, J. P., Mottahedeh, J., Pyle, A. D., Wu, H. and Kornblum, H. I. (2011) Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell 8, 59-71.   DOI
20 Kwon, K. J., Kim, J. N., Kim, M. K., Lee, J., Ignarro, L. J., Kim, H. J., Shin, C. Y. and Han, S. H. (2011) Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. J. Pineal. Res. 50, 110-123.
21 Li, X., Ying, G. G., Zhao, J. L., Chen, Z. F., Lai, H. J. and Su, H. C. (2013) 4-Nonylphenol, bisphenol-A and triclosan levels in human urine of children and students in China, and the effects of drinking these bottled materials on the levels. Environ. Int. 52, 81-86.   DOI
22 Oliveira, R., Domingues, I., Koppe Grisolia, C. and Soares, A. M. (2009) Effects of triclosan on zebrafish early-life stages and adults. Environ. Sci. Pollut. Res. Int. 16, 679-688.   DOI
23 Orvos, D. R., Versteeg, D. J., Inauen, J., Capdevielle, M., Rothenstein, A. and Cunningham, V. (2002) Aquatic toxicity of triclosan. Environ. Toxicol. Chem. 21, 1338-1349.   DOI
24 Paik, J. H., Ding, Z., Narurkar, R., Ramkissoon, S., Muller, F., Kamoun, W. S., Chae, S. S., Zheng, H., Ying, H. and Mahoney, J. (2009) FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell 5, 540-553.   DOI
25 Paul, K. B., Hedge, J. M., DeVito, M. J. and Crofton, K. M. (2010) Developmental triclosan exposure decreases maternal and neonatal thyroxine in rats. Environ. Toxicol. Chem. 29, 2840-2844.   DOI
26 Sandborgh-Englund, G., M. Adolfsson-Erici., Odham, G. and Ekstrand, J. (2006). Pharmacokinetics of triclosan following oral ingestion in humans. J. Toxicol. Environ. Health A 69, 1861-1873.   DOI
27 Prevention, C. f. D. C. a. (2015) Fourth National Report on Human Exposure to Environmental Chemicals. http://www.cdc.gov/exposurereport/.
28 Renault, V. M., Rafalski, V. A., Morgan, A. A., Salih, D. A., Brett, J. O., Webb, A. E., Villeda, S. A., Thekkat, P. U., Guillerey, C. and Denko, N. C. (2009) FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5, 527-539.   DOI
29 Rodriguez, P. E. and Sanchez, M. S. (2010) Maternal exposure to triclosan impairs thyroid homeostasis and female pubertal development in Wistar rat offspring. J. Toxicol. Environ Health A. 73, 1678-1688.   DOI
30 SCCS (2010) Opinion on triclosan (antimicrobial resistance) European Commission.
31 Suller, M. and Russell, A. (2000) Triclosan and antibiotic resistance in Staphylococcus aureus. J. Antimicrob Chemother. 46, 11-18.
32 Szychowski, K. A., Sitarz, A. M. and Wojtowicz, A. K. (2015) Triclosan induces Fas receptor-dependent apoptosis in mouse neocortical neurons in vitro. Neuroscience 284, 192-201.   DOI
33 Veldhoen, N., Skirrow, R. C., Osachoff, H., Wigmore, H., Clapson, D. J., Gunderson, M. P., Van Aggelen, G. and Helbing, C. C. (2006) The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development. Aquat. Toxicol. 80, 217-227.   DOI
34 Wang, L.-Q., Falany, C. N. and James, M. O. (2004) Triclosan as a substrate and inhibitor of 3′-phosphoadenosine 5′-phosphosulfatesulfotransferase and UDP-glucuronosyl transferase in human liver fractions. Drug Metab. Dispos. 32, 1162-1169.   DOI
35 Zhou, D., Shao, L. and Spitz, D. R. (2014) Reactive oxygen species in normal and tumor stem cells. Adv. Cancer Res. 122, 1-67.   DOI
36 Wu, Y., Beland, F. A., Chen, S. and Fang, J. L. (2014) Extracellular signal- regulated kinases 1/2 and Akt contribute to triclosan-stimulated proliferation of JB6 Cl 41-5a cells. Arch. Toxicol. 1-15.
37 Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J. and Greenberg, M. E. (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326-1331.   DOI