AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress
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 ske...
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| Veröffentlicht in: | Nephrology, dialysis, transplantation dialysis, transplantation, 2015-06, Vol.30 (6), p.934-942 |
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| creator | Nishikawa, Mikito Ishimori, Naoki Takada, Shingo Saito, Akimichi Kadoguchi, Tomoyasu Furihata, Takaaki Fukushima, Arata Matsushima, Shouji Yokota, Takashi Kinugawa, Shintaro Tsutsui, Hiroyuki |
| description | 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.
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.
Plasma IS levels were significantly increased in CKD compared with Sham (1.05 ± 0.11 versus 0.21 ± 0.03 mg/dL, P |
| doi_str_mv | 10.1093/ndt/gfv103 |
| format | Article |
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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.
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 + AST-120 (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.
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.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfv103</identifier><identifier>PMID: 25878055</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Carbon - pharmacology ; Indican - pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - physiology ; Myoblasts - cytology ; Myoblasts - drug effects ; Myoblasts - metabolism ; Oxidation-Reduction ; Oxidative Stress - drug effects ; Oxides - pharmacology ; Physical Conditioning, Animal ; Quality of Life ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - pathology ; Renal Insufficiency, Chronic - prevention & control ; Superoxides - metabolism</subject><ispartof>Nephrology, dialysis, transplantation, 2015-06, Vol.30 (6), p.934-942</ispartof><rights>The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c367t-ea333e5b8e489327a00d940ee2b5f4f91e2d494c398908db5d65f25138f05ff3</citedby><cites>FETCH-LOGICAL-c367t-ea333e5b8e489327a00d940ee2b5f4f91e2d494c398908db5d65f25138f05ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25878055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishikawa, Mikito</creatorcontrib><creatorcontrib>Ishimori, Naoki</creatorcontrib><creatorcontrib>Takada, Shingo</creatorcontrib><creatorcontrib>Saito, Akimichi</creatorcontrib><creatorcontrib>Kadoguchi, Tomoyasu</creatorcontrib><creatorcontrib>Furihata, Takaaki</creatorcontrib><creatorcontrib>Fukushima, Arata</creatorcontrib><creatorcontrib>Matsushima, Shouji</creatorcontrib><creatorcontrib>Yokota, Takashi</creatorcontrib><creatorcontrib>Kinugawa, Shintaro</creatorcontrib><creatorcontrib>Tsutsui, Hiroyuki</creatorcontrib><title>AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress</title><title>Nephrology, dialysis, transplantation</title><addtitle>Nephrol Dial Transplant</addtitle><description>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.
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.
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 + AST-120 (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.
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.</description><subject>Animals</subject><subject>Carbon - pharmacology</subject><subject>Indican - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - physiology</subject><subject>Myoblasts - cytology</subject><subject>Myoblasts - drug effects</subject><subject>Myoblasts - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxides - pharmacology</subject><subject>Physical Conditioning, Animal</subject><subject>Quality of Life</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Renal Insufficiency, Chronic - prevention & control</subject><subject>Superoxides - metabolism</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kc1O3DAUha2qVRloNzwA8rKqFPBPnNhLhKAgIXXR2UeOfT3jkthT2xmYB-p71mgoq7s43z1n8SF0TsklJYpfBVuuNm5PCf-AVrTtSMO4FB_Rqoa0IYKoE3Sa829CiGJ9_xmdMCF7SYRYob_Xv9YNZQTrGSYfky6Q8RSfIYHF8ALJ-AzY6J02vhywDhbPvkSzjcEmryc8-riBANln7AMuW8D5CSYoNZqXbCbALsW5PhnAz75ssdmmGLzBT94GOGBb-3Wd2HuN6-ZifNjg-OKtLn5fy0qCnL-gT05PGb6-3TO0vrtd39w3jz9_PNxcPzaGd31pQHPOQYwSWqk46zUhVrUEgI3CtU5RYLZVreFKKiLtKGwnHBOUS0eEc_wMfTvW7lL8s0Auw-yzgWnSAeKSB9pJJmXXd7Si34-oSTHnBG7YJT_rdBgoGV6tDNXKcLRS4Yu33mWcwb6j_zXwf-L4jLU</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Nishikawa, Mikito</creator><creator>Ishimori, Naoki</creator><creator>Takada, Shingo</creator><creator>Saito, Akimichi</creator><creator>Kadoguchi, Tomoyasu</creator><creator>Furihata, Takaaki</creator><creator>Fukushima, Arata</creator><creator>Matsushima, Shouji</creator><creator>Yokota, Takashi</creator><creator>Kinugawa, Shintaro</creator><creator>Tsutsui, Hiroyuki</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201506</creationdate><title>AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress</title><author>Nishikawa, Mikito ; Ishimori, Naoki ; Takada, Shingo ; Saito, Akimichi ; Kadoguchi, Tomoyasu ; Furihata, Takaaki ; Fukushima, Arata ; Matsushima, Shouji ; Yokota, Takashi ; Kinugawa, Shintaro ; Tsutsui, Hiroyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-ea333e5b8e489327a00d940ee2b5f4f91e2d494c398908db5d65f25138f05ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Carbon - pharmacology</topic><topic>Indican - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - physiology</topic><topic>Myoblasts - cytology</topic><topic>Myoblasts - drug effects</topic><topic>Myoblasts - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxides - pharmacology</topic><topic>Physical Conditioning, Animal</topic><topic>Quality of Life</topic><topic>Renal Insufficiency, Chronic - metabolism</topic><topic>Renal Insufficiency, Chronic - pathology</topic><topic>Renal Insufficiency, Chronic - prevention & control</topic><topic>Superoxides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishikawa, Mikito</creatorcontrib><creatorcontrib>Ishimori, Naoki</creatorcontrib><creatorcontrib>Takada, Shingo</creatorcontrib><creatorcontrib>Saito, Akimichi</creatorcontrib><creatorcontrib>Kadoguchi, Tomoyasu</creatorcontrib><creatorcontrib>Furihata, Takaaki</creatorcontrib><creatorcontrib>Fukushima, Arata</creatorcontrib><creatorcontrib>Matsushima, Shouji</creatorcontrib><creatorcontrib>Yokota, Takashi</creatorcontrib><creatorcontrib>Kinugawa, Shintaro</creatorcontrib><creatorcontrib>Tsutsui, Hiroyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishikawa, Mikito</au><au>Ishimori, Naoki</au><au>Takada, Shingo</au><au>Saito, Akimichi</au><au>Kadoguchi, Tomoyasu</au><au>Furihata, Takaaki</au><au>Fukushima, Arata</au><au>Matsushima, Shouji</au><au>Yokota, Takashi</au><au>Kinugawa, Shintaro</au><au>Tsutsui, Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><addtitle>Nephrol Dial Transplant</addtitle><date>2015-06</date><risdate>2015</risdate><volume>30</volume><issue>6</issue><spage>934</spage><epage>942</epage><pages>934-942</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><abstract>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.
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.
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 + AST-120 (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.
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.</abstract><cop>England</cop><pmid>25878055</pmid><doi>10.1093/ndt/gfv103</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nephrology, dialysis, transplantation, 2015-06, Vol.30 (6), p.934-942 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Carbon - pharmacology Indican - pharmacology Male Mice Mice, Inbred C57BL Muscle, Skeletal - drug effects Muscle, Skeletal - physiology Myoblasts - cytology Myoblasts - drug effects Myoblasts - metabolism Oxidation-Reduction Oxidative Stress - drug effects Oxides - pharmacology Physical Conditioning, Animal Quality of Life Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - pathology Renal Insufficiency, Chronic - prevention & control Superoxides - metabolism |
| title | 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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