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CREATINE SUPPLEMENTATION ATTENUATES PULMONARY AND SYSTEMIC EFFECTS OF LUNG ISCHEMIA AND REPERFUSION INJURY
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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 50
-
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, Crþsham, I/R, and CrþI/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 o 0.05), total cells (p o 0.01),
and neutrophils (p o 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p o 0.001).
The levels of interleukin-1β (p o 0.05), tissue damping, and tissue elastance (p o 0.05) were also
minimized. Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid,p o 0.001; histologic edema index, p o 0.001) and neutrophils accumulation in lung tissue (p o 0.001).
As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p o 0.05),
reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue
(p o 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 antioxidant
properties of Cr and modulation of TLRs.
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