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Mar. Drugs 2017, 15(7), 225; doi:10.3390/md15070225

Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK1

1
Department of Environmental Sciences, Faculty of Life and Environmental Science, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan
2
The Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Minato, Tokyo 108-8477, Japan
*
Author to whom correspondence should be addressed.
Received: 17 May 2017 / Revised: 7 July 2017 / Accepted: 10 July 2017 / Published: 17 July 2017
(This article belongs to the Special Issue Tetrodotoxin)
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Abstract

This study examined the urinary excretion of tetrodotoxin (TTX) modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK1. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA), l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH), and unaffected by 1-methyl-4-phenylpyridinium (MPP+), oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs) and organic cation/carnitine transporters (OCTNs), partially transported by organic anion transporters (OATs) and multidrug resistance-associated proteins (MRPs), and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs). View Full-Text
Keywords: tetrodotoxin; urinary excretion; food poisoning; LLC-PK1; transcellular transport; organic cation transporter; organic cation/carnitine transporter; organic anion transporter; multidrug resistance-associated protein tetrodotoxin; urinary excretion; food poisoning; LLC-PK1; transcellular transport; organic cation transporter; organic cation/carnitine transporter; organic anion transporter; multidrug resistance-associated protein
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Matsumoto, T.; Ishizaki, Y.; Mochizuki, K.; Aoyagi, M.; Mitoma, Y.; Ishizaki, S.; Nagashima, Y. Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK1. Mar. Drugs 2017, 15, 225.

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