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: Francine Maria Almeida, Manoel Carneiro Oliveira-Junior, Renato Aparecido Souza, Ricardo Costa Petroni, Sonia Fatima Soto, Francisco Garcia Soriano, Paulo Tarso Camillo de Carvalho, Regiane Albertini, Nilsa Regina Damaceno-Rodrigues, Fernanda Degobbi Tenorio Quirino Santos Lopes, Hugo Caire Castro-Faria-Neto, Milton Arruda Martins, Marisa Dolhnikoff, Rogerio Pazetti, Rodolfo Paula Vieira
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 35 Issue 2 Pg. 242-50 (Feb 2016) ISSN: 1557-3117 [Electronic] United States
• PMID: 26215332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Toll-Like Receptors
• Nitric Oxide
• Insulin-Like Growth Factor I
• Creatine

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Antioxidants
• Apoptosis (drug effects)
• Blotting, Western
• Creatine (administration & dosage)
• Dietary Supplements
• Immunohistochemistry
• Inflammation (prevention & control)
• Insulin-Like Growth Factor I (analysis)
• Ischemia (drug therapy)
• Lung (blood supply, drug effects)
• Male
• Nitric Oxide (analysis)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy)
• Toll-Like Receptors (analysis)