Abstract
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.
Highlights
Chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in world
In light of the findings described above, we hypothesize that crocin induces GSH Synthesis via Nuclear erythroid-related factor 2 (Nrf2) dependent mechanisms and attenuates cigarette smoke-induced COPD mediated oxidative stress in lung tissue that leads to cardiac dysfunctions
Confirmation of CS-induced lung injuries model in rat With the purpose of establishing the model of CS- induced COPD, the rats were exposed to cigarette smoke for 8-weeks
Summary
Chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in world. The aim of this study was to investigate the protective role of crocin against CSE-mediated oxidative stress, inflammatory process, Nrf modifications and impairment of cardiac function in rats with COPD. There is overwhelming evidence that oxidative stress plays an essential role in the pathogenesis of COPD [2] This oxidative damage to cellular organelles plays a central role in mediating a wide array of downstream processes that contribute to the development and progression of COPD. Increased oxidative stress in the respiratory compartment of COPD patients originates from the increased burden of oxidants from environmental exposures such as air pollutants, cigarette smoke (CS), and increased amounts of reactive oxygen species (ROS) released from inflammatory cells involved in the destructive inflammatory process in the lungs of COPD subjects [5]. Exposure of macrophages and lymphocytes to oxidative stress results in release various inflammatory substances including cytokines and chemokines, which could destroy collagen and elastin, stimulate mucosal secretions in lung tissues, and even lead to more destructive processes in lungs [6]
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