Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling
Purpose The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats. Methods Wistar rats were randomly assigned into three groups ( n = 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TC...
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| Veröffentlicht in: | European journal of nutrition 2020-03, Vol.59 (2), p.661-669 |
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| creator | Cella, Paola S. Marinello, Poliana C. Borges, Fernando H. Ribeiro, Diogo F. Chimin, Patrícia Testa, Mayra T. J. Guirro, Philippe B. Duarte, José A. Cecchini, Rubens Guarnier, Flávia A. Deminice, Rafael |
| description | Purpose
The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats.
Methods
Wistar rats were randomly assigned into three groups (
n
= 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals’ weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin–proteasome pathways were also evaluated using real-time PCR and immunoblotting.
Results
The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy.
Conclusion
Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis. |
| doi_str_mv | 10.1007/s00394-019-01933-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2186149691</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2185982085</sourcerecordid><originalsourceid>FETCH-LOGICAL-c441t-528ffcc14fc41a790c4a67df8fc25d35f58d810dc303c66e9397e2f4138128d23</originalsourceid><addsrcrecordid>eNp9kUuLFDEUhYMozkP_gAsJuHFTmlelUktpfAwMuFFchnRy09ZMkiqTlNA_x39qemocwYWLkJvwnXMuHIReUPKGEjK8LYTwUXSEjqfDeScfoXMquOwko_3jh5kMZ-iilBtCCOOSPkVnnCgih0Gco1-7DKZOCXBZlyVAhFTbe054SvibCbeQO9ZLXNc4524PJk_pgLOpBS8Zfja64HILAaoJOK7FBsCm5nn5fsT7YxsrpPUUcMDlWCrEyTZnH0yMW4xJrjnNFVqeg0M2bvsv0yGZ0HTP0BNvQoHn9_cl-vrh_Zfdp-7688er3bvrzgpBa9cz5b21VHgrqBlGYoWRg_PKW9Y73vteOUWJs5xwKyWMfByAeUG5okw5xi_R6823bfNjhVJ1nIqFEEyCeS2aUSWpGOVIG_rqH_RmXnNb947qR8WI6hvFNsrmuZQMXi95iiYfNSX6VKDeCtStPH1XoJZN9PLeet1HcA-SP401gG9AWU5VQP6b_R_b31xYqdE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2185982085</pqid></control><display><type>article</type><title>Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Cella, Paola S. ; Marinello, Poliana C. ; Borges, Fernando H. ; Ribeiro, Diogo F. ; Chimin, Patrícia ; Testa, Mayra T. J. ; Guirro, Philippe B. ; Duarte, José A. ; Cecchini, Rubens ; Guarnier, Flávia A. ; Deminice, Rafael</creator><creatorcontrib>Cella, Paola S. ; Marinello, Poliana C. ; Borges, Fernando H. ; Ribeiro, Diogo F. ; Chimin, Patrícia ; Testa, Mayra T. J. ; Guirro, Philippe B. ; Duarte, José A. ; Cecchini, Rubens ; Guarnier, Flávia A. ; Deminice, Rafael</creatorcontrib><description>Purpose
The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats.
Methods
Wistar rats were randomly assigned into three groups (
n
= 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals’ weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin–proteasome pathways were also evaluated using real-time PCR and immunoblotting.
Results
The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy.
Conclusion
Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.</description><identifier>ISSN: 1436-6207</identifier><identifier>EISSN: 1436-6215</identifier><identifier>DOI: 10.1007/s00394-019-01933-6</identifier><identifier>PMID: 30806774</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Atrophy ; Body weight ; Body weight loss ; Carcinoma 256, Walker - metabolism ; Chemistry ; Chemistry and Materials Science ; Creatine ; Creatine - administration & dosage ; Creatine - pharmacology ; Dietary Supplements ; Disease Models, Animal ; Drinking water ; Food intake ; Immunoblotting ; Inflammation ; Inflammation - prevention & control ; Interleukin 6 ; Male ; Muscle, Skeletal - drug effects ; Muscular Atrophy - prevention & control ; Musculoskeletal system ; Nutrition ; Original Contribution ; Oxidative stress ; Proteasomes ; Proteolysis ; Proteolysis - drug effects ; Rats ; Rats, Wistar ; Signal Transduction - drug effects ; Skeletal muscle ; Spleen ; T cell receptors ; Tumor cells ; Tumor necrosis factor-α ; Ubiquitin ; Water intake ; White pulp</subject><ispartof>European journal of nutrition, 2020-03, Vol.59 (2), p.661-669</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>European Journal of Nutrition is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-528ffcc14fc41a790c4a67df8fc25d35f58d810dc303c66e9397e2f4138128d23</citedby><cites>FETCH-LOGICAL-c441t-528ffcc14fc41a790c4a67df8fc25d35f58d810dc303c66e9397e2f4138128d23</cites><orcidid>0000-0002-9246-1079</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00394-019-01933-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00394-019-01933-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30806774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cella, Paola S.</creatorcontrib><creatorcontrib>Marinello, Poliana C.</creatorcontrib><creatorcontrib>Borges, Fernando H.</creatorcontrib><creatorcontrib>Ribeiro, Diogo F.</creatorcontrib><creatorcontrib>Chimin, Patrícia</creatorcontrib><creatorcontrib>Testa, Mayra T. J.</creatorcontrib><creatorcontrib>Guirro, Philippe B.</creatorcontrib><creatorcontrib>Duarte, José A.</creatorcontrib><creatorcontrib>Cecchini, Rubens</creatorcontrib><creatorcontrib>Guarnier, Flávia A.</creatorcontrib><creatorcontrib>Deminice, Rafael</creatorcontrib><title>Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling</title><title>European journal of nutrition</title><addtitle>Eur J Nutr</addtitle><addtitle>Eur J Nutr</addtitle><description>Purpose
The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats.
Methods
Wistar rats were randomly assigned into three groups (
n
= 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals’ weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin–proteasome pathways were also evaluated using real-time PCR and immunoblotting.
Results
The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy.
Conclusion
Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.</description><subject>Animals</subject><subject>Atrophy</subject><subject>Body weight</subject><subject>Body weight loss</subject><subject>Carcinoma 256, Walker - metabolism</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Creatine</subject><subject>Creatine - administration & dosage</subject><subject>Creatine - pharmacology</subject><subject>Dietary Supplements</subject><subject>Disease Models, Animal</subject><subject>Drinking water</subject><subject>Food intake</subject><subject>Immunoblotting</subject><subject>Inflammation</subject><subject>Inflammation - prevention & control</subject><subject>Interleukin 6</subject><subject>Male</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscular Atrophy - prevention & control</subject><subject>Musculoskeletal system</subject><subject>Nutrition</subject><subject>Original Contribution</subject><subject>Oxidative stress</subject><subject>Proteasomes</subject><subject>Proteolysis</subject><subject>Proteolysis - drug effects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Signal Transduction - drug effects</subject><subject>Skeletal muscle</subject><subject>Spleen</subject><subject>T cell receptors</subject><subject>Tumor cells</subject><subject>Tumor necrosis factor-α</subject><subject>Ubiquitin</subject><subject>Water intake</subject><subject>White pulp</subject><issn>1436-6207</issn><issn>1436-6215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUuLFDEUhYMozkP_gAsJuHFTmlelUktpfAwMuFFchnRy09ZMkiqTlNA_x39qemocwYWLkJvwnXMuHIReUPKGEjK8LYTwUXSEjqfDeScfoXMquOwko_3jh5kMZ-iilBtCCOOSPkVnnCgih0Gco1-7DKZOCXBZlyVAhFTbe054SvibCbeQO9ZLXNc4524PJk_pgLOpBS8Zfja64HILAaoJOK7FBsCm5nn5fsT7YxsrpPUUcMDlWCrEyTZnH0yMW4xJrjnNFVqeg0M2bvsv0yGZ0HTP0BNvQoHn9_cl-vrh_Zfdp-7688er3bvrzgpBa9cz5b21VHgrqBlGYoWRg_PKW9Y73vteOUWJs5xwKyWMfByAeUG5okw5xi_R6823bfNjhVJ1nIqFEEyCeS2aUSWpGOVIG_rqH_RmXnNb947qR8WI6hvFNsrmuZQMXi95iiYfNSX6VKDeCtStPH1XoJZN9PLeet1HcA-SP401gG9AWU5VQP6b_R_b31xYqdE</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Cella, Paola S.</creator><creator>Marinello, Poliana C.</creator><creator>Borges, Fernando H.</creator><creator>Ribeiro, Diogo F.</creator><creator>Chimin, Patrícia</creator><creator>Testa, Mayra T. J.</creator><creator>Guirro, Philippe B.</creator><creator>Duarte, José A.</creator><creator>Cecchini, Rubens</creator><creator>Guarnier, Flávia A.</creator><creator>Deminice, Rafael</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7QP</scope><scope>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9246-1079</orcidid></search><sort><creationdate>20200301</creationdate><title>Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling</title><author>Cella, Paola S. ; Marinello, Poliana C. ; Borges, Fernando H. ; Ribeiro, Diogo F. ; Chimin, Patrícia ; Testa, Mayra T. J. ; Guirro, Philippe B. ; Duarte, José A. ; Cecchini, Rubens ; Guarnier, Flávia A. ; Deminice, Rafael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-528ffcc14fc41a790c4a67df8fc25d35f58d810dc303c66e9397e2f4138128d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Atrophy</topic><topic>Body weight</topic><topic>Body weight loss</topic><topic>Carcinoma 256, Walker - metabolism</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Creatine</topic><topic>Creatine - administration & dosage</topic><topic>Creatine - pharmacology</topic><topic>Dietary Supplements</topic><topic>Disease Models, Animal</topic><topic>Drinking water</topic><topic>Food intake</topic><topic>Immunoblotting</topic><topic>Inflammation</topic><topic>Inflammation - prevention & control</topic><topic>Interleukin 6</topic><topic>Male</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscular Atrophy - prevention & control</topic><topic>Musculoskeletal system</topic><topic>Nutrition</topic><topic>Original Contribution</topic><topic>Oxidative stress</topic><topic>Proteasomes</topic><topic>Proteolysis</topic><topic>Proteolysis - drug effects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Signal Transduction - drug effects</topic><topic>Skeletal muscle</topic><topic>Spleen</topic><topic>T cell receptors</topic><topic>Tumor cells</topic><topic>Tumor necrosis factor-α</topic><topic>Ubiquitin</topic><topic>Water intake</topic><topic>White pulp</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cella, Paola S.</creatorcontrib><creatorcontrib>Marinello, Poliana C.</creatorcontrib><creatorcontrib>Borges, Fernando H.</creatorcontrib><creatorcontrib>Ribeiro, Diogo F.</creatorcontrib><creatorcontrib>Chimin, Patrícia</creatorcontrib><creatorcontrib>Testa, Mayra T. J.</creatorcontrib><creatorcontrib>Guirro, Philippe B.</creatorcontrib><creatorcontrib>Duarte, José A.</creatorcontrib><creatorcontrib>Cecchini, Rubens</creatorcontrib><creatorcontrib>Guarnier, Flávia A.</creatorcontrib><creatorcontrib>Deminice, Rafael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Career & Technical Education Database</collection><collection>Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cella, Paola S.</au><au>Marinello, Poliana C.</au><au>Borges, Fernando H.</au><au>Ribeiro, Diogo F.</au><au>Chimin, Patrícia</au><au>Testa, Mayra T. J.</au><au>Guirro, Philippe B.</au><au>Duarte, José A.</au><au>Cecchini, Rubens</au><au>Guarnier, Flávia A.</au><au>Deminice, Rafael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling</atitle><jtitle>European journal of nutrition</jtitle><stitle>Eur J Nutr</stitle><addtitle>Eur J Nutr</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>59</volume><issue>2</issue><spage>661</spage><epage>669</epage><pages>661-669</pages><issn>1436-6207</issn><eissn>1436-6215</eissn><abstract>Purpose
The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats.
Methods
Wistar rats were randomly assigned into three groups (
n
= 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals’ weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin–proteasome pathways were also evaluated using real-time PCR and immunoblotting.
Results
The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy.
Conclusion
Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30806774</pmid><doi>10.1007/s00394-019-01933-6</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9246-1079</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1436-6207 |
| ispartof | European journal of nutrition, 2020-03, Vol.59 (2), p.661-669 |
| issn | 1436-6207 1436-6215 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Animals Atrophy Body weight Body weight loss Carcinoma 256, Walker - metabolism Chemistry Chemistry and Materials Science Creatine Creatine - administration & dosage Creatine - pharmacology Dietary Supplements Disease Models, Animal Drinking water Food intake Immunoblotting Inflammation Inflammation - prevention & control Interleukin 6 Male Muscle, Skeletal - drug effects Muscular Atrophy - prevention & control Musculoskeletal system Nutrition Original Contribution Oxidative stress Proteasomes Proteolysis Proteolysis - drug effects Rats Rats, Wistar Signal Transduction - drug effects Skeletal muscle Spleen T cell receptors Tumor cells Tumor necrosis factor-α Ubiquitin Water intake White pulp |
| title | Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling |
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