title: Creatine supplementation prevents hyperhomocysteinemia, oxidative stress and cancer-induced cachexia progression in Walker-256 tumor-bearing rats.
abstract: The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr). A life span experiment was conducted as the third experiment. Creatine was supplied in drinking water for 21 days (8 g/L) in all cases. Tumor implantation consisted of a suspension of Walker-256 cells (8.0 × 10(7) cells in 0.5 mL of PBS). The progressive increase (P < 0.05) in tumor mass coincided with a progressively lower body weight and higher hepatic oxidative stress; plasma Hcy concentration was 80 % higher (P < 0.05) by 10 days of tumor implantation. Impaired Hcy metabolism was evidenced by decreased hepatic betaine-homocysteine methyltransferase (Bhmt), glycine N-methyltransferase (Gnmt) and cystathionine beta synthase (CBS) gene expression. In contrast, creatine supplementation promoted a 28 % reduction of tumor weight (P < 0.05). Plasma Hcy (C 6.1 ± 0.6, T 10.3 ± 1.5, TCr 6.3 ± 0.9, µmol/L) and hepatic oxidative stress were lower in the TCr group compared to T. Creatine supplementation was unable to decrease Hcy concentration and to increase SAM/SAH ratio in tumor tissue. These data suggest that creatine effects on hepatic impaired Hcy metabolism promoted by tumor cell inoculation are responsible to decrease plasma Hcy in tumor-bearing rats. In conclusion, Walker-256 tumor growth is associated with progressive hyperhomocysteinemia, body weight loss and liver oxidative stress in rats. Creatine supplementation, however, prevented these tumor-associated perturbations.
authors.affiliation: 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, PR, Brazil. rdeminice@yahoo.com.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Deminice
authors.affiliation: 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, PR, Brazil.
authors.forename: Paola Sanches
authors.initials: PS
authors.lastname: Cella
authors.affiliation: 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, PR, Brazil.
authors.forename: Camila S
authors.initials: CS
authors.lastname: Padilha
authors.affiliation: Department of Pathology, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Fernando H
authors.initials: FH
authors.lastname: Borges
authors.affiliation: Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lilian Eslaine Costa Mendes
authors.initials: LE
authors.lastname: da Silva
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Patrícia L
authors.initials: PL
authors.lastname: Campos-Ferraz
authors.affiliation: Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Alceu Afonso
authors.initials: AA
authors.lastname: Jordao
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Jason Lorne
authors.initials: JL
authors.lastname: Robinson
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Bertolo
authors.affiliation: Department of Pathology, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Cecchini
authors.affiliation: Department of Pathology, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Flávia Alessandra
authors.initials: FA
authors.lastname: Guarnier
mesh_terms: D000818:Animals; D002100:Cachexia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003401:Creatine / Q000493:pharmacokinetics / Q000494:pharmacology*; D020138:Hyperhomocysteinemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003401:Creatine
keywords: Cancer; Creatine; Homocysteine; Oxidative stress; Rats