Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury

详细信息    查看全文

• 作者：Francine Maria Almeida ; MS^a ; Manoel Carneiro Oliveira-Junior ; BSc^b ; Renato Aparecido Souza ; PhD^b ; ^c ; Ricardo Costa Petroni ; PhD^d ; Sonia Fatima Soto ; MS^a ; Francisco Garcia Soriano ; MD PhD^d ; Paulo Tarso Camillo de Carvalho ; PhD^b ; Regiane Albertini ; PhD^b ; Nilsa Regina Damaceno-Rodrigues ; PhD^e ; Fernanda Degobbi Tenorio Quirino Santos Lopes ; PhD^a ; Hugo Caire Castro-Faria-Neto ; MD ; PhD^f ; Milton Arruda Martins ; MD ; PhD^a ; Marisa Dolhnikoff ; MD ; PhD^g ; Rogerio Pazetti ; PhD^h ; Rodolfo Paula Vieira ; PhD^b ; ^{rodrelena@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：creatine supplementation ; ischemia/reperfusion ; inflammation ; oxidative stress ; lung function
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：35
• 期：2
• 页码：242-250
• 全文大小：2547 K

文摘

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.