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AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress

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Title: AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress
Authors: Nishikawa, Mikito Browse this author
Ishimori, Naoki Browse this author →KAKEN DB
Takada, Shingo Browse this author →KAKEN DB
Saito, Akimichi Browse this author
Kadoguchi, Tomoyasu Browse this author
Furihata, Takaaki Browse this author
Fukushima, Arata Browse this author
Matsushima, Shouji Browse this author
Yokota, Takashi Browse this author →KAKEN DB
Kinugawa, Shintaro Browse this author →KAKEN DB
Tsutsui, Hiroyuki Browse this author →KAKEN DB
Keywords: AST-120
chronic kidney disease
exercise capacity
indoxyl sulfate
mitochondria
skeletal muscle
Issue Date: Jun-2015
Publisher: Oxford University Press
Journal Title: Nephrology dialysis transplantation
Volume: 30
Issue: 6
Start Page: 934
End Page: 942
Publisher DOI: 10.1093/ndt/gfv103
PMID: 25878055
Abstract: Background. Exercise capacity and quality of life are markedly impaired in chronic kidney disease (CKD). Increased plasma uremic toxins such as indoxyl sulfate (IS), which induce oxidative stress, may be involved in this process. An oral adsorbent, AST-120, can reduce circulating IS, however, its effects on skeletal muscle and exercise capacity have not been investigated in CKD. Methods. Subtotal-nephrectomy or sham operation was performed in 8-week-old C57BL/6J mice. They were divided into two groups with or without 8% (w/w) of AST-120 in standard diet for 20 weeks. Sham, Sham + AST-120, CKD and CKD + AST-120 (n = 12, each group) were studied. We also conducted a C2C12 cell culture study to determine the direct effects of IS on oxidative stress. Results. Plasma IS levels were significantly increased in CKD compared with Sham (1.05 +/- 0.11 versus 0.21 +/- 0.03 mg/dL, P < 0.05), which was significantly ameliorated in CKD + AST120 (0.41 +/- 0.06 mg/dL). The running distance to exhaustion determined by treadmill tests was significantly reduced in CKD compared with Sham (267 +/- 17 versus 427 +/- 36 m, P < 0.05), and this reduction was also significantly ameliorated in CKD + AST-120 (407 +/- 38 m) without altering skeletal muscle weight. Citrate synthase activity and mitochondrial biogenesis gene were downregulated, and superoxide production was significantly increased in the skeletal muscle from CKD, and these changes were normalized in CKD + AST-120. Incubation of C2C12 cells with IS significantly increased NAD(P) H oxidase activity. Conclusions. The administration of AST-120 improved exercise capacity and mitochondrial biogenesis of skeletal muscle via reducing oxidative stress. AST-120 may be a novel therapeutic agent against exercise intolerance in CKD.
Rights: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Nephrology Dialysis Transplantation following peer review. The version of record "Nishikawa M, Ishimori N, Takada S, et al. AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress. Nephrol Dial Transplant. 2015 Jun;30(6):934-42" is available online at: http://doi.org/10.1093/ndt/gfv103
Type: article (author version)
URI: http://hdl.handle.net/2115/61332
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石森 直樹

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