title: Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury.
abstract: BACKGROUND
  Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage. This study evaluated the effects of Cr supplementation in a model of lung I/R.
  
  
  METHODS
  Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response.
  
  
  RESULTS
  Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleukin-1β (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized. Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001).
  
  
  CONCLUSIONS
  Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and anti-oxidant properties of Cr and modulation of TLRs.
authors.affiliation: Department of Clinical Medicine (LIM 20), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Francine Maria
authors.initials: FM
authors.lastname: Almeida
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE), São Paulo, São Paulo, Brazil.
authors.forename: Manoel Carneiro
authors.initials: MC
authors.lastname: Oliveira-Junior
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE), São Paulo, São Paulo, Brazil; Grupo de Estudos e Pesquisa em Ciência da Saúde (GEP-CS), Instituto Federal de Educação, Ciência e Tecnologia do Sul de Minas Gerais (IFSULDEMINAS), Campus Muzambinho, Muzambinho, Minas Gerais, Brazil.
authors.forename: Renato Aparecido
authors.initials: RA
authors.lastname: Souza
authors.affiliation: Department of Clinical Medicine (LIM 51), School of Medicine University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Ricardo Costa
authors.initials: RC
authors.lastname: Petroni
authors.affiliation: Department of Clinical Medicine (LIM 20), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Sonia Fatima
authors.initials: SF
authors.lastname: Soto
authors.affiliation: Department of Clinical Medicine (LIM 51), School of Medicine University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE), São Paulo, São Paulo, Brazil.
authors.forename: Paulo Tarso Camillo de
authors.initials: PT
authors.lastname: Carvalho
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE), São Paulo, São Paulo, Brazil.
authors.forename: Regiane
authors.initials: R
authors.lastname: Albertini
authors.affiliation: Department of Pathology (LIM 59), School of Medicine University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Nilsa Regina
authors.initials: NR
authors.lastname: Damaceno-Rodrigues
authors.affiliation: Department of Clinical Medicine (LIM 20), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Fernanda Degobbi Tenorio Quirino Santos
authors.initials: FD
authors.lastname: Lopes
authors.affiliation: Laboratory of Immunopharmacology, Oswaldo Cruz Foundation, Oswaldo Cruz Institute, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Hugo Caire
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.affiliation: Department of Clinical Medicine (LIM 20), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Milton Arruda
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Department of Pathology (LIM 05), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolhnikoff
authors.affiliation: Department of Cardiopneumology (LIM 61), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Rogerio
authors.initials: R
authors.lastname: Pazetti
authors.affiliation: Laboratory of Pulmonary and Exercise Immunology (LABPEI), Nove de Julho University (UNINOVE), São Paulo, São Paulo, Brazil. Electronic address: rodrelena@yahoo.com.br.
authors.forename: Rodolfo Paula
authors.initials: RP
authors.lastname: Vieira
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003401:Creatine / Q000008:administration & dosage*; D019587:Dietary Supplements; D007150:Immunohistochemistry; D007249:Inflammation / Q000517:prevention & control; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007511:Ischemia / Q000188:drug therapy*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D051193:Toll-Like Receptors / Q000032:analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D003401:Creatine
keywords: creatine supplementation; inflammation; ischemia/reperfusion; lung function; oxidative stress