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-1ß (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.
Subject(s)
Creatine/administration & dosage , Ischemia/drug therapy , Lung/blood supply , Reperfusion Injury/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Antioxidants , Apoptosis/drug effects , Blotting, Western , Dietary Supplements , Immunohistochemistry , Inflammation/prevention & control , Insulin-Like Growth Factor I/analysis , Lung/drug effects , Male , Nitric Oxide/analysis , Rats , Rats, Wistar , Toll-Like Receptors/analysisABSTRACT
This study aimed to verify the development of placental and systemic inflammation in rats exposed to fine particulate matter before or during pregnancy. Wistar rats were exposed to filtered air (control) or to a load of 600 µg/m(3) of fine particles in the air. The gene expression of IL-1ß, IL-4, IL-6, IL-10, INF-γ, TNF-α and Toll-like receptor 4 in the placenta was evaluated. The serum and placental concentrations of IL-1ß, IL-4, IL-6, IL-10, INF-γ and TNF-α were measured. The total and differential blood leukocyte and blood platelet count was assessed. Compared to control animals, IL-4 content was elevated in the fetal portion of the placenta in rats exposed to air pollution before and during pregnancy. Increased IL-4 suggests that a placental inflammatory reaction may have occurred in response to exposure to fine particulate matter and that this cytokine was responsible, among possibly others factors, for resolution of the inflammatory reaction.