BackgroundChronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in world. Cigarette smoke is known to cause oxidative stress and deplete glutathione (GSH) levels. Nuclear erythroid-related factor 2 (Nrf2) is involved in transcriptional regulation of glutamate-cysteine ligase catalytic subunit (GCLc). Antioxidant compounds may be of therapeutic value in monitoring disease progression. Crocin demonstrates antioxidant and anti-inflammatory functions. The aim of this study was to investigate the protective role of crocin against CSE-mediated oxidative stress, inflammatory process, Nrf2 modifications and impairment of cardiac function in rats with COPD.MethodsEighty rats were divided into four groups: Control, Cigarette smoke exposure (CSE), Crocin, Crocin+CS. Each group was divided into the two parts: 1) to evaluate lung inflammatory and oxidative process, 2) to evaluate the effect of Cigarette smoke induced-lung injuries on cardiac electrocardiogram (such as heart rate and QRS complex) and hemodynamic parameters (such as perfusion pressure and left ventricular developed pressure).ResultsCSE rats showed a significant increase in cotinine concentration (17.24 ng/ml), and inflammatory parameters and a decrease in PO2 (75.87 mmHg) and expression of PKC (0.86 fold), PI3K (0.79 fold), MAPK (0.87 fold), Nrf2 (0.8 fold) and GCLc (0.75 fold) genes, antioxidant activity, and finally cardiac abnormalities in electrocardiogram and hemodynamic parameters. Co-treatment whit crocin could restore all these values to normal levels.ConclusionsCS induced-COPD in rat model provides evidence that chronic CS exposure leads to lung injury and mediated cardiac dysfunction. Crocin co-treatment by modulating of Nrf2 pathway protected lung injury caused by COPD and its related cardiac dysfunction. In this study, we showed the importance of Nrf2 activators as a therapeutic target for the development of novel therapy for lung oxidative injuries.

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Background and objective: Oxidative stress is a process that occurs through free radicals on the cell membranes which causes damage to the cell and intracellular organelles especially mitochondria membranes. H2O2 induced oxidative stress in human cells is of interest in toxicological research since oxidative stress plays a main role in the etiology of several pathological conditions. Neutrophil Elastase (Serine proteinase) is involved in the pathology process of emphysema as a respiratory disease through lung in ammation, and destruction of alveolar walls. The present study investigated the direct oxidative stress effects of Elastase in comparison with H2O2 on human lung epithelial cells (A549 cells) in relation to the generation of reactive oxygen species (ROS) and modulation of oxidation resistance 1 (OXR1) and its downstream pathway using the well-known antioxidant Ellagic acid as an activator of antioxidant genes.Materials and methods: The human pulmonary epithelial cells (A549) were divided into the 9 groups including: Negative control, Positive control (H2O2), Elastase (15, 30, and 60 mU/ml), Ellagic acid (10 μmol/L), and Elastase+Ellagic acid. Cytotoxicity, reactive oxygen spices generation, oxidative stress pro le, level of reactive metabolites, and gene expression of OXR1 and its downstream genes were measured in all groups.Results: The obtained data demonstrated that Elastase exposure caused to oxidative stress damage in a dose-depended manner which was associated with decreases in antioxidant defense system genes.Conversely, treatment with Ellagic acid as a potent antioxidant showed improved antioxidant enzyme activity and content which was in line with the upregulation of OXR1 signaling pathway genes.Conclusions: The present ndings can highlight the novel mechanism underlying the oxidative stress induces by Neutrophil Elastase through OXR1 and related genes. Moreover, the bene t of Ellagic acid on cytoprotection, resulting from its antioxidant properties was documented.