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Toxins 2018, 10(1), 19; https://doi.org/10.3390/toxins10010019

Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques

1
Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai 980-8578, Japan
2
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
3
Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan
4
Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan
5
Division of Feto-Maternal Medical Science, Department of Community Medical Support, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8574, Japan
6
Division of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai 980-8578, Japan
7
Division of Integrative Renal Replacement Therapy, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
8
Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8574, Japan
9
Shubun University, Ichinomiya 491-0938, Japan
*
Author to whom correspondence should be addressed.
Received: 31 October 2017 / Revised: 14 December 2017 / Accepted: 26 December 2017 / Published: 28 December 2017
(This article belongs to the Special Issue Uremia and Cardiovascular Disease)
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Abstract

Elevated circulating uremic toxins are associated with a variety of symptoms and organ dysfunction observed in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are representative uremic toxins that exert various harmful effects. We recently showed that IS induces metabolic alteration in skeletal muscle and causes sarcopenia in mice. However, whether organ-specific accumulation of IS and PCS is associated with tissue dysfunction is still unclear. We investigated the accumulation of IS and PCS using liquid chromatography/tandem mass spectrometry in various tissues from mice with adenine-induced CKD. IS and PCS accumulated in all 15 organs analyzed, including kidney, skeletal muscle, and brain. We also visualized the tissue accumulation of IS and PCS with immunohistochemistry and mass spectrometry imaging techniques. The oral adsorbent AST-120 prevented some tissue accumulation of IS and PCS. In skeletal muscle, reduced accumulation following AST-120 treatment resulted in the amelioration of renal failure-associated muscle atrophy. We conclude that uremic toxins can accumulate in various organs and that AST-120 may be useful in treating or preventing organ dysfunction in CKD, possibly by reducing tissue accumulation of uremic toxins. View Full-Text
Keywords: uremic toxin; chronic kidney disease; indoxyl sulfate; p-cresyl sulfate; mass spectrometry uremic toxin; chronic kidney disease; indoxyl sulfate; p-cresyl sulfate; mass spectrometry
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Sato, E.; Saigusa, D.; Mishima, E.; Uchida, T.; Miura, D.; Morikawa-Ichinose, T.; Kisu, K.; Sekimoto, A.; Saito, R.; Oe, Y.; Matsumoto, Y.; Tomioka, Y.; Mori, T.; Takahashi, N.; Sato, H.; Abe, T.; Niwa, T.; Ito, S. Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques. Toxins 2018, 10, 19.

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