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Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease

Although many experimental studies have shown the favorable effects of zonisamide on mitochondria using models of Parkinson’s disease (PD), the influence of zonisamide on metabolism in PD patients remains unclear. To assess metabolic status under zonisamide treatment in PD, we performed a pilot stud...

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Autores principales: Ueno, Shin-Ichi, Saiki, Shinji, Fujimaki, Motoki, Takeshige-Amano, Haruka, Hatano, Taku, Oyama, Genko, Ishikawa, Kei-Ichi, Yamaguchi, Akihiro, Nojiri, Shuko, Akamatsu, Wado, Hattori, Nobutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356654/
https://www.ncbi.nlm.nih.gov/pubmed/30597973
http://dx.doi.org/10.3390/cells8010014
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author Ueno, Shin-Ichi
Saiki, Shinji
Fujimaki, Motoki
Takeshige-Amano, Haruka
Hatano, Taku
Oyama, Genko
Ishikawa, Kei-Ichi
Yamaguchi, Akihiro
Nojiri, Shuko
Akamatsu, Wado
Hattori, Nobutaka
author_facet Ueno, Shin-Ichi
Saiki, Shinji
Fujimaki, Motoki
Takeshige-Amano, Haruka
Hatano, Taku
Oyama, Genko
Ishikawa, Kei-Ichi
Yamaguchi, Akihiro
Nojiri, Shuko
Akamatsu, Wado
Hattori, Nobutaka
author_sort Ueno, Shin-Ichi
collection PubMed
description Although many experimental studies have shown the favorable effects of zonisamide on mitochondria using models of Parkinson’s disease (PD), the influence of zonisamide on metabolism in PD patients remains unclear. To assess metabolic status under zonisamide treatment in PD, we performed a pilot study using a comprehensive metabolome analysis. Plasma samples were collected for at least one year from 30 patients with PD: 10 without zonisamide medication and 20 with zonisamide medication. We performed comprehensive metabolome analyses of plasma with capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. We also measured disease severity using Hoehn and Yahr (H&Y) staging and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor section, and analyzed blood chemistry. In PD with zonisamide treatment, 15 long-chain acylcarnitines (LCACs) tended to be increased, of which four (AC(12:0), AC(12:1)-1, AC(16:1), and AC(16:2)) showed statistical significance. Of these, two LCACs (AC(16:1) and AC(16:2)) were also identified by partial least squares analysis. There was no association of any LCAC with age, disease severity, levodopa daily dose, or levodopa equivalent dose. Because an upregulation of LCACs implies improvement of mitochondrial β-oxidation, zonisamide might be beneficial for mitochondrial β-oxidation, which is suppressed in PD.
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spelling pubmed-63566542019-02-06 Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease Ueno, Shin-Ichi Saiki, Shinji Fujimaki, Motoki Takeshige-Amano, Haruka Hatano, Taku Oyama, Genko Ishikawa, Kei-Ichi Yamaguchi, Akihiro Nojiri, Shuko Akamatsu, Wado Hattori, Nobutaka Cells Article Although many experimental studies have shown the favorable effects of zonisamide on mitochondria using models of Parkinson’s disease (PD), the influence of zonisamide on metabolism in PD patients remains unclear. To assess metabolic status under zonisamide treatment in PD, we performed a pilot study using a comprehensive metabolome analysis. Plasma samples were collected for at least one year from 30 patients with PD: 10 without zonisamide medication and 20 with zonisamide medication. We performed comprehensive metabolome analyses of plasma with capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. We also measured disease severity using Hoehn and Yahr (H&Y) staging and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor section, and analyzed blood chemistry. In PD with zonisamide treatment, 15 long-chain acylcarnitines (LCACs) tended to be increased, of which four (AC(12:0), AC(12:1)-1, AC(16:1), and AC(16:2)) showed statistical significance. Of these, two LCACs (AC(16:1) and AC(16:2)) were also identified by partial least squares analysis. There was no association of any LCAC with age, disease severity, levodopa daily dose, or levodopa equivalent dose. Because an upregulation of LCACs implies improvement of mitochondrial β-oxidation, zonisamide might be beneficial for mitochondrial β-oxidation, which is suppressed in PD. MDPI 2018-12-29 /pmc/articles/PMC6356654/ /pubmed/30597973 http://dx.doi.org/10.3390/cells8010014 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ueno, Shin-Ichi
Saiki, Shinji
Fujimaki, Motoki
Takeshige-Amano, Haruka
Hatano, Taku
Oyama, Genko
Ishikawa, Kei-Ichi
Yamaguchi, Akihiro
Nojiri, Shuko
Akamatsu, Wado
Hattori, Nobutaka
Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease
title Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease
title_full Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease
title_fullStr Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease
title_full_unstemmed Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease
title_short Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson’s Disease
title_sort zonisamide administration improves fatty acid β-oxidation in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356654/
https://www.ncbi.nlm.nih.gov/pubmed/30597973
http://dx.doi.org/10.3390/cells8010014
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