Effects of Chinese green tea on cigarette smoke-induced oxidative stress, inflammation and proteases/anti-proteases in rat lung in vivo

Abstract

of thesis entitled Effects of Chinese green tea on cigarette smoke-induced oxidative stress, inflammation and proteases/anti-proteases in rat lung in vivo Submitted by John K.H. CHAN for the degree of Doctor of Philosophy at the University of Hong Kong in October, 2010 Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of diseases composed of chronic bronchitis, emphysema and small airway remodeling. COPD is a slowly progressive and largely irreversible condition characterized by airway obstruction. The exact mechanism of COPD pathogenesis is not yet clear, but oxidative stress, chronic inflammation along with the imbalance of proteases/anti-proteases are the major components involved in disease progression. There is now renewed interest in the underlying cellular and molecular mechanisms of COPD that could lead to new therapeutic treatments. Cigarette smoke (CS) is the major contributor to COPD pathogenesis, resulting from the burden of oxidants in CS. Indeed, COPD can also occur in lifelong non-smokers. However, a much higher proportion of smokers may develop abnormal lung functions at some point if they continue to smoke. In establishing the CS-exposed rat model, we demonstrated that CS could induce both local and systemic oxidative stress, reflected by elevation of lung antioxidant enzymes and serum oxidative stress marker. We also observed increased levels of pro-inflammatory mediators like tumor necrosis factor (TNF)-, interleukin (IL)-1, IL-6 and cytokine-induced neutrophil chemoattractant (CINC)-1 in lung homogenates and C-reactive protein (CRP) in systemic circulation, as well as the elevation of neutrophil elastase (NE) and matrix metalloproteinase (MMP)-12 activities in bronchoalveolar lavage (BAL) and lung homogenates. Structurally, we observed an airspace enlargement and mucus-secreting goblet cell hyperplasia which is resembled to some clinical features in COPD patients. Pretreatment of Chinese green tea, freshly brewed from dried Lung Chen tea leaves, could prevent CS-induced lung injury possibly by scavenging reactive oxygen species (ROS), leading to a significant reduction of IL-6 in lung homogenates and serum CRP as well as protease activities in BAL and lung homogenates. For adiponectin known to possess anti-inflammatory property, one of the major adipokines released from adipose tissues, it has shown to be responsible for emphysema-like development in mice. Nonetheless, its exact function remains controversial. In the rat model, we found significant reduction in serum and BAL adiponectin levels after 56-day CS exposure and Chinese green tea had no significant reversal effect. In contrast, we observed significant elevated adiponectin levels in plasma from COPD patients compared to healthy ever-smokers. Plasma adiponectin levels were inversely correlated with force expiratory volume in one second (FEV1; % predicted) after adjustment for age, BMI, smoking status and pack-years smoked. These findings suggested that adiponectin might be related to the pathogenesis or progression of COPD over time. In summary, our study provides a platform for elucidating the pathogenesis of COPD and for testing potential therapeutic agents. Chinese green tea is one of the most common beverages consumed in Southeast Asia and in some Western countries. Our results suggested Chinese green tea might be able to slow down CS-induced disease progression, and daily consumption of Chinese green tea might be beneficial to CS-induced chronic lung diseases such as COPD, which will become the fourth leading cause of death by 2030 worldwide.