ABSTRACT
Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The current study examined the expression of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric oxide synthase (iNOS) respectively, in patients with severe COPD and control smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was quantified in peripheral lung. HO-1+ alveolar macrophages were decreased in severe COPD compared to control smokers, whereas no difference was observed in iNOS+ macrophages. In contrast, severe patients had significantly higher numbers of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2 pneumocytes and their number was inversely related to HO-1+ macrophages. There were no significant differences in N-Tyr immunostaining between the two groups. However, the rate of protein nitration in lung tissue was directly related to iNOS expression and associated with lower values of forced expiratory volume in one second/forced vital capacity. HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD. In conclusion, the results suggest that the enzymes involved in the oxidative stress response may have a different role in the lung defence and that imbalance between haem oxygenase-1 and inducible nitric oxide synthase may be associated with the development of severe impairment in chronic obstructive pulmonary disease patients.
Subject(s)
Heme Oxygenase (Decyclizing)/analysis , Lung/chemistry , Lung/pathology , Nitric Oxide Synthase/analysis , Pulmonary Disease, Chronic Obstructive/enzymology , Pulmonary Disease, Chronic Obstructive/pathology , Tyrosine/analogs & derivatives , Aged , Female , Heme Oxygenase-1 , Humans , Lung/enzymology , Macrophages, Alveolar/enzymology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/pathology , Male , Membrane Proteins , Middle Aged , Nitric Oxide Synthase Type II , Oxidative Stress/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Respiratory Function Tests , Severity of Illness Index , Tyrosine/analysisABSTRACT
Tyrosine kinase inhibition and tumor growth inhibition activity of verbascoside and homoplantaginin are described. Both molecules proved to be equally significant inhibitors of isolated EGF-R tyrosine kinases, nevertheless their in vitro antiproliferative activity was variable in cellular assays. Their different inhibitory efficacies could be interpreted on the basis of conformational analysis and lipophilicity evaluation.
