Abstract
Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF) leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase) activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway.
Highlights
Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions, such as lung transplantation, pulmonary thrombolysis, and postresuscitation for cardiac arrest, which results in interstitial edema, inflammatory cell infiltration, alveolar-capillary barrier leakage, and gas exchange impairment [1,2,3]
Accumulating experimental evidence proves that the development of oxidative stress induced by the production of reactive oxygen species (ROS) and decreased activity of antioxidant enzyme plays a pivotal role in the etiopathogenesis of I/R
The I/R group had significantly damaged alveoli structure with interstitial edema, evident inflammatory cell infiltration, and alveolar bleeding. These pathological changes were significantly alleviated in the maresin 1 (MaR 1) + I/R group as compared with those seen in the I/R group (P < 0 05)
Summary
Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions, such as lung transplantation, pulmonary thrombolysis, and postresuscitation for cardiac arrest, which results in interstitial edema, inflammatory cell infiltration, alveolar-capillary barrier leakage, and gas exchange impairment [1,2,3]. The underlying molecular mechanisms are not fully understood, and ways to prevent lung I/R injury are still lacking. Many mechanisms, such as sterile immunity, oxidative stress, complement activation, endothelial dysfunction, overactivation of coagulation pathways, and excessive cell death, contribute to the pathogenesis of ischemia/reperfusion [5]. Accumulating experimental evidence proves that the development of oxidative stress induced by the production of reactive oxygen species (ROS) and decreased activity of antioxidant enzyme plays a pivotal role in the etiopathogenesis of I/R. Reactive oxygen species activate subsequent excess leukocyte accumulation and cascades of inflammation, causing severe lung damage [6, 7]. Protecting the lung from oxidative stress could be an ideal method for ameliorating lung I/R injury
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