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Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver
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| Title: | Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver |
| Authors: | Yamada, Yuma Browse this author →KAKEN DB | | Nakamura, Kohei Browse this author | | Abe, Jiro Browse this author | | Hyodo, Mamoru Browse this author →KAKEN DB | | Haga, Sanae Browse this author →KAKEN DB | | Ozaki, Michitaka Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | Mitochondria | | Mitochondrial delivery | | Antioxidant chemicals | | Coenzyme Q(10) | | Ischemia/reperfusion injury | | MITO-Porter | | In vivo delivery |
| Issue Date: | 10-Sep-2015 |
| Publisher: | Elsevier |
| Journal Title: | Journal of controlled release |
| Volume: | 213 |
| Start Page: | 86 |
| End Page: | 95 |
| Publisher DOI: | 10.1016/j.jconrel.2015.06.037 |
| PMID: | 26160304 |
| Abstract: | We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q(10) (CoQ(10)), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ(10) in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ(10)-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ(10)-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ(10)-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria. Finally, we applied the optimized CoQ(10) -MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ(10)-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ(10) via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies. (C) 2015 Elsevier B.V. All rights reserved. |
| Rights: | © 2015, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/62775 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 山田 勇磨
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