Literature DB >> 25404284

The commonly used antimicrobial additive triclosan is a liver tumor promoter.

Mei-Fei Yueh1, Koji Taniguchi2, Shujuan Chen1, Ronald M Evans3, Bruce D Hammock4, Michael Karin2, Robert H Tukey5.   

Abstract

Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a synthetic, broad-spectrum antibacterial chemical used in a wide range of consumer products including soaps, cosmetics, therapeutics, and plastics. The general population is exposed to TCS because of its prevalence in a variety of daily care products as well as through waterborne contamination. TCS is linked to a multitude of health and environmental effects, ranging from endocrine disruption and impaired muscle contraction to effects on aquatic ecosystems. We discovered that TCS was capable of stimulating liver cell proliferation and fibrotic responses, accompanied by signs of oxidative stress. Through a reporter screening assay with an array of nuclear xenobiotic receptors (XenoRs), we found that TCS activates the nuclear receptor constitutive androstane receptor (CAR) and, contrary to previous reports, has no significant effect on mouse peroxisome proliferation activating receptor α (PPARα). Using the procarcinogen diethylnitrosamine (DEN) to initiate tumorigenesis in mice, we discovered that TCS substantially accelerates hepatocellular carcinoma (HCC) development, acting as a liver tumor promoter. TCS-treated mice exhibited a large increase in tumor multiplicity, size, and incidence compared with control mice. TCS-mediated liver regeneration and fibrosis preceded HCC development and may constitute the primary tumor-promoting mechanism through which TCS acts. These findings strongly suggest there are adverse health effects in mice with long-term TCS exposure, especially on enhancing liver fibrogenesis and tumorigenesis, and the relevance of TCS liver toxicity to humans should be evaluated.

Entities:  

Keywords:  hepatocellular carcinoma; liver fibrosis; triclosan; tumor promoter

Mesh:

Substances:

Year:  2014        PMID: 25404284      PMCID: PMC4260592          DOI: 10.1073/pnas.1419119111

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  40 in total

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Review 3.  Liver fibrogenesis: a new role for the renin-angiotensin system.

Authors:  Ramón Bataller; Pau Sancho-Bru; Pere Ginès; David A Brenner
Journal:  Antioxid Redox Signal       Date:  2005 Sep-Oct       Impact factor: 8.401

4.  Caveolin-1 is essential for liver regeneration.

Authors:  Manuel A Fernández; Cecilia Albor; Mercedes Ingelmo-Torres; Susan J Nixon; Charles Ferguson; Teymuras Kurzchalia; Francesc Tebar; Carlos Enrich; Robert G Parton; Albert Pol
Journal:  Science       Date:  2006-09-15       Impact factor: 47.728

5.  Interleukin 8 in human hepatocellular carcinoma correlates with cancer cell invasion of vessels but not with tumor angiogenesis.

Authors:  Fumitake Kubo; Shinichi Ueno; Kiyokazu Hiwatashi; Masahiko Sakoda; Koichi Kawaida; Kensuke Nuruki; Takashi Aikou
Journal:  Ann Surg Oncol       Date:  2005-08-09       Impact factor: 5.344

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Authors:  F Xavier Bosch; Josepa Ribes; Mireia Díaz; Ramon Cléries
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7.  Percutaneous penetration and dermal metabolism of triclosan (2,4, 4'-trichloro-2'-hydroxydiphenyl ether).

Authors:  T Moss; D Howes; F M Williams
Journal:  Food Chem Toxicol       Date:  2000-04       Impact factor: 6.023

8.  Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression.

Authors:  Ali Canbay; Ariel E Feldstein; Hajime Higuchi; Nate Werneburg; Annette Grambihler; Steve F Bronk; Gregory J Gores
Journal:  Hepatology       Date:  2003-11       Impact factor: 17.425

9.  Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production.

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Journal:  Science       Date:  2007-07-06       Impact factor: 47.728

Review 10.  Recent evidence regarding triclosan and cancer risk.

Authors:  Michael T Dinwiddie; Paul D Terry; Jiangang Chen
Journal:  Int J Environ Res Public Health       Date:  2014-02-21       Impact factor: 3.390

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  57 in total

1.  Topical Application of the Antimicrobial Agent Triclosan Induces NLRP3 Inflammasome Activation and Mitochondrial Dysfunction.

Authors:  Lisa M Weatherly; Hillary L Shane; Sherri A Friend; Ewa Lukomska; Rachel Baur; Stacey E Anderson
Journal:  Toxicol Sci       Date:  2020-07-01       Impact factor: 4.849

2.  The amplification of risk in experimental diffusion chains.

Authors:  Mehdi Moussaïd; Henry Brighton; Wolfgang Gaissmaier
Journal:  Proc Natl Acad Sci U S A       Date:  2015-04-20       Impact factor: 11.205

3.  Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition.

Authors:  Juyoung K Shim; Molly A Caron; Lisa M Weatherly; Logan B Gerchman; Suraj Sangroula; Siham Hattab; Alan Y Baez; Talya J Briana; Julie A Gosse
Journal:  J Appl Toxicol       Date:  2019-08-19       Impact factor: 3.446

4.  Twisting electrospun nanofiber fine strips into functional sutures for sustained co-delivery of gentamicin and silver.

Authors:  Shixuan Chen; Liangpeng Ge; Aubrey Mueller; Mark A Carlson; Matthew J Teusink; Franklin D Shuler; Jingwei Xie
Journal:  Nanomedicine       Date:  2017-02-06       Impact factor: 5.307

Review 5.  Small-molecule modulators of the constitutive androstane receptor.

Authors:  Milu T Cherian; Sergio C Chai; Taosheng Chen
Journal:  Expert Opin Drug Metab Toxicol       Date:  2015-05-15       Impact factor: 4.481

6.  Comparison of hepatotoxicity and mechanisms induced by triclosan (TCS) and methyl-triclosan (MTCS) in human liver hepatocellular HepG2 cells.

Authors:  Lu Wang; Boyu Mao; Huixin He; Yu Shang; Yufang Zhong; Zhiqiang Yu; Yiting Yang; Hui Li; Jing An
Journal:  Toxicol Res (Camb)       Date:  2018-10-12       Impact factor: 3.524

7.  Association of birth outcomes with fetal exposure to parabens, triclosan and triclocarban in an immigrant population in Brooklyn, New York.

Authors:  Laura A Geer; Benny F G Pycke; Joshua Waxenbaum; David M Sherer; Ovadia Abulafia; Rolf U Halden
Journal:  J Hazard Mater       Date:  2016-03-11       Impact factor: 10.588

Review 8.  Small-molecule modulators of PXR and CAR.

Authors:  Sergio C Chai; Milu T Cherian; Yue-Ming Wang; Taosheng Chen
Journal:  Biochim Biophys Acta       Date:  2016-02-24

9.  Triclosan disrupts immune cell function by depressing Ca2+ influx following acidification of the cytoplasm.

Authors:  Suraj Sangroula; Alan Y Baez Vasquez; Prakash Raut; Bright Obeng; Juyoung K Shim; Grace D Bagley; Bailey E West; John E Burnell; Marissa S Kinney; Christian M Potts; Sasha R Weller; Joshua B Kelley; Samuel T Hess; Julie A Gosse
Journal:  Toxicol Appl Pharmacol       Date:  2020-08-21       Impact factor: 4.219

10.  An immunoassay for the detection of triclosan-O-glucuronide, a primary human urinary metabolite of triclosan.

Authors:  Anupama Ranganathan; Shirley J Gee; Bruce D Hammock
Journal:  Anal Bioanal Chem       Date:  2015-08-09       Impact factor: 4.142

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