Quercetin Attenuates Acute Lung Injury Caused by Cigarette Smoke Both In Vitro and In Vivo.

Cigarette smoke is highly toxic and is a major risk factor for airway inflammation, oxidative stress, and decline in lung function-the starting points for chronic obstructive pulmonary disease. Quercetin is a potent dietary antioxidant that displays anti-inflammatory activities. The goal of this study was to evaluate the effects of quercetin on reducing the redox imbalance and inflammation induced by short-term cigarette smoke exposure. In vitro, 25 and 50 µM quercetin attenuated the effects of cigarette smoke extract (increased generation of reactive oxygen species and nitric oxide) on J774A.1 cells (macrophages). We further examined the effects of quercetin in vivo. Male C57Bl/6 mice that received 10 mg/kg/day of quercetin via orogastric gavage before exposure to five days of cigarette smoke demonstrated reduced levels of leukocyte, oxidative stress, histological pattern changes of pulmonary parenchyma, and lung function alterations compared to the group that did not receive quercetin. These results suggest that quercetin may be an effective adjuvant for treating the effects of cigarette smoke exposure.

Inflammatory and oxidative stress biomarkers induced by silica exposure in crystal craftsmen.

BACKGROUND: Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica. METHODS: A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO2- ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO). RESULTS: Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis. CONCLUSION: CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples.

Oxidative stress in mouse plasma and lungs induced by cigarette smoke and lipopolysaccharide.

Short-term exposure to cigarette smoke (CS) or lipopolysaccharide (LPS) leads to acute lung inflammation through oxidant-antioxidant imbalance. We studied the response in mice exposed to smoke or LPS during five consecutive days, as measured by superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, as well as lipid peroxidation and nitric oxide levels in bronchoalveolar lavage fluid (BALF), lung homogenates, and plasma. Control mice were exposed to ambient air. Exposure to CS or LPS led to a similar influx of alveolar macrophages and neutrophils into the BALF; however, hydroxyproline levels were increased only in the CS group (p<0.001); SOD activity was increased in the BALF (p<0.001) and lung homogenates (p<0.05) of the CS group but was decreased in the BALF (p<0.05), lung homogenates (p<0.05) and plasma (p<0.01) of the LPS group. CAT activity was increased in the BALF (p<0.01), lung homogenates (p<0.001) and plasma (p<0.05) of the CS group but decreased in the BALF (p<0.001) and plasma (p<0.05) of the LPS group. GPx activity was reduced in the BALF (p<0.01) and plasma (p<0.01) of both the CS and LPS groups. Lipid peroxidation was increased in the BALF (p<0.001) and lung homogenates (p<0.001) of the CS group. Finally, the levels of nitrite were reduced in the CS (p<0.01) and LPS (p<0.001) groups. Our data show that the activity profiles of enzymes contributing to oxidant-antioxidant imbalance in the lungs differ depending on the inflammatory stimulus, and that SOD, CAT and GPx may be useful markers of oxidative stress in acute lung inflammation induced by exposure to CS.

Alpha-tocopherol and ascorbic acid supplementation reduced acute lung inflammatory response by cigarette smoke in mouse.

OBJECTIVE: Short-term cigarette smoke (CS) exposure leads to acute lung inflammation through its influence over oxidants/antioxidants imbalance. Antioxidant vitamins such as ascorbic acid and alpha-tocopherol interact with oxidizing radicals. It is not clear if antioxidant supplementation can reduce inflammatory lung responses. Thus our aim was to analyze the effects of vitamin supplementation on the lungs of mice exposed to six cigarettes per day with histologic, cytological, and biochemical methods. METHODS: C57BL/6 mice were exposed to ambient air (control) or CS from 3, 6, 9, 12, or 15 cigarettes daily for up to 5 d. Mice alveolar macrophages and polymorphonuclear cells were counted in the bronchoalveolar lavage. Groups of CS animals received 50 mg/kg of ascorbic acid daily and/or 50 mg/kg of alpha-tocopherol daily as an oral supplementation (CS+C, CS+E, CS+C+E, respectively) 12 h before CS exposure. Thiobarbituric acid-reactive substances were detected and western blot to nuclear factor-kappaB were performed in lung extracts; metalloprotease-12 and tumor necrosis factor-alpha positive alveolar macrophages were quantified in the lungs processed for immunohistochemistry of the animals exposed to the smoke from six cigarettes daily for 5 d. RESULTS: The number of alveolar macrophages and polymorphonuclear cells in bronchoalveolar lavage (cells x 10(3)/mL) in mice exposed to CS were increased and CS with vitamin supplementation groups presented bronchoalveolar lavage cells similar to those of control. Thiobarbituric acid-reactive substances values were reduced in vitamin supplementation groups when compared with CS and the lower value was found in the CS+C+E group. Metalloprotease-12 and tumor necrosis factor-alpha were more evident in CS as much as nuclear factor-kappaB activation when compared with control and vitamin supplementation groups. CONCLUSION: Our results showed that CS induced acute lung inflammation. The inflammatory process after cigarette exposures was reduced by ascorbic acid, alpha-tocopherol, or more efficiently by both vitamin supplementations.