Journal Article Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Yamada, Yuma  ,  Nakamura, Kohei  ,  Abe, Jiro  ,  Hyodo, Mamoru  ,  Haga, Sanae  ,  Ozaki, Michitaka  ,  Harashima, Hideyoshi

213pp.86 - 95 , 2015-09-10 , Elsevier
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.

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