4.5 Article

Triclosan is a mitochondrial uncoupler in live zebrafish

期刊

JOURNAL OF APPLIED TOXICOLOGY
卷 36, 期 12, 页码 1662-1667

出版社

WILEY
DOI: 10.1002/jat.3311

关键词

triclosan; irgasan; zebrafish; seahorse bioscience; oxygen consumption rate; ATP production; bioenergetics; proton leak; Extracellular Flux Analyzer; mitochondrial uncoupler

资金

  1. National Institute of Environmental Health Sciences of the National Institute of Health [R15ES24593]

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Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here, we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24-hour post-fertilization (hpf) zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, after acute exposure to TCS, the basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96-well assay format. The method developed in this study provides a high-throughput tool to identify previously unknown mitochondrial uncouplers in a living organism. Copyright (c) 2016 John Wiley & Sons, Ltd. Antimicrobial agent triclosan (TCS) is a mitochondrial uncoupler in multiple cell types. Here, we present data, obtained with a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer, indicating that TCS is also a mitochondrial uncoupler in living zebrafish [24hour post-fertilization (hpf); 1 embryo per well]. TCS increases the oxygen consumption rate and proton leak and decreases ATP-linked respiration and spare respiratory capacity without affecting survival or heartbeat rate. These data indicate, for the first time, that TCS is a mitochondrial uncoupler in vivo.

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