Paola S Cella1, Poliana C Marinello1,2, Fernando H Borges2, Diogo F Ribeiro1, Patrícia Chimin1, Mayra T J Testa1, Philippe B Guirro1, José A Duarte3, Rubens Cecchini2, Flávia A Guarnier2, Rafael Deminice4. 1. Department of Physical Education, Faculty of Physical Education and Sport, State University of Londrina, Rodovia Celso Garcia Cid, Pr 445 Km 380, Campus Universitário, Londrina, Paraná, Brazil. 2. Department of General Pathology, State University of Londrina, Londrina, PR, Brazil. 3. University of Porto, CIAFEL, Faculty of Sport, Porto, Portugal. 4. Department of Physical Education, Faculty of Physical Education and Sport, State University of Londrina, Rodovia Celso Garcia Cid, Pr 445 Km 380, Campus Universitário, Londrina, Paraná, Brazil. rdeminice@uel.br.
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.
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.
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