Effects of cigarette smoke in mice with different levels of alpha(1)-proteinase inhibitor and sensitivity to oxidants.
ABSTRACT The role of strain difference in the response to cigarette smoke was investigated in mice. Mice of the strains DBA/2 and C57BL/6J responded to acute cigarette smoke with a decrease of the antioxidant defenses of their bronchoalveolar lavage (BAL) fluids. On the other hand, under these conditions ICR mice increased their BAL antioxidant defenses. Mice of these three strains were then exposed to cigarette smoke (three cigarettes/d, 5 d/wk) for 7 mo. Lung elastin content was significantly decreased in C57BL/6J and DBA/2 but not in ICR mice. Also, emphysema, assessed morphometrically using three methods, was present in C57BL/6J and DBA/2 but not in ICR mice. In an additional study pallid mice, with a severe serum alpha(1)-proteinase inhibitor (alpha(1)-PI) deficiency and that develop spontaneous emphysema, were exposed to cigarette smoke for 4 mo. This resulted in an acceleration of the development of the spontaneous emphysema assessed with morphometrical and biochemical (lung elastin content) methods. All these results indicate that sensitivity to the effects of cigarette smoke is strain-dependent and cigarette smoke accelerates the effects of alpha(1)-PI deficiency.
- SourceAvailable from: Luís Cristóvão Porto[Show abstract] [Hide abstract]
ABSTRACT: Short-term cigarette smoke exposure has been associated with acute lung inflammation (ALI) and oxidative damage. We studied mate tea (Ilex paraguariensis infusion) as a possible nutritional resource for ALI. C57BL/6 mice (n = 30) were administered with mate tea orally (150 mg/kg, CSMO), mate tea intraperitonially (150 mg/kg, CSMIP), or the vehicle (CS) and then exposed to cigarette smoke for 5 d (six cigarettes per day). The control group was sham-smoked (n = 30). One day after the final exposure, mice were sacrificed. Bronchoalveolar lavages were performed and lungs removed for biochemical (lung homogenates) and histologic analyses. Mate tea reduced the increase of alveolar macrophages and neutrophils in bronchoalveolar lavages (cells x 10(3)/mL) of the CSMO (214.3 +/- 21.4 and 12.2 +/- 4.9) and CSMIP (248.3 +/- 11.1 and 12.1 +/- 2.3) groups compared with the CS group (425.9 +/- 28.1 and 140.5 +/- 20.1). Mate tea reduced lipid peroxidation (the control group was considered 100%) and tumor necrosis factor-alpha (picograms per milliliter) in the CSMO group (61.3 +/- 11.3 and 185.3 +/- 21.8) compared with the CS group (150.0 +/- 18.1 and 242.3 +/- 13.2). Matrix metalloprotease-9 activity was higher in the CS group and lower in the CSMO group. Oxidative and inflammatory markers in the CSMO group were not different from those in the control group. These data imply a potential antioxidant role for mate tea on ALI. Further studies are needed to determine such mechanisms and to explore its potential as an anti-inflammatory and nutritional resource in lung damaged by cigarette smoke exposure.Nutrition 05/2008; 24(4):375-81. DOI:10.1016/j.nut.2008.01.002 · 3.05 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun.Mass Spectrometry Reviews 01/2005; 24(1):55-99. DOI:10.1002/mas.20006 · 8.05 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: We examined nuclear factor kappaB activation, release of inflammatory mediators and cellular infiltration in acute cigarette smoke inflammation models. One hour after exposure to one puff of cigarette smoke, alveolar macrophages from bronchoalveolar lavage (BAL) fluid of C57BL/6J mice showed an increased activity of nuclear factor kappaB-DNA binding but similar numbers as compared to that of BAL fluid from mice exposed to ambient air. Exposure to 1 cigarette/day for 1, 4 or 7 days led to an increase in interleukin-1beta and monocyte chemoattractant protein-1 levels and to a progressive influx of nuclear factor kappaB-activated alveolar macrophages into the BAL fluid and lung tissue. Exposure to 2 cigarettes/day for 7 days led to a significant increase in interleukin-1beta levels accompanied by a massive alveolar macrophage influx into the BAL fluid. Tumor necrosis factor-alpha levels and subsequent neutrophil influx were only detected after exposure to 4 or 8 cigarettes/day for 7 days. Treatment of mice with an antibody anti-interleukin-1beta during cigarette smoke exposure for 7 days significantly reduced both interleukin-1beta levels and alveolar macrophage influx. These data show that a single exposure to cigarette smoke rapidly activates alveolar macrophages, inducing the production of interleukin-1beta, which may play an important role in triggering chronic cigarette smoke-mediated lung inflammation.European Journal of Pharmacology 10/2004; 498(1-3):279-86. DOI:10.1016/j.ejphar.2004.07.047 · 2.68 Impact Factor