Abstract

Background: During inspiration the lung is exposed to numerous oxidantsand therefore has developed a system of antioxidant defense. This organ, besides the liver, is the majorsource of glutathione (GSH) metabolism, from which type II pneumocytes are metabolically the most activecells. Material/Methods: To analyze oxidative stress, rats were exposed to air (control) or to 10 ppmnitrogen dioxide (NO(2)) for 3 and 20 days to induce acute and chronic lung injury. As measure of oxidativestress, GSH/GSSG ratios in blood, bronchoalveolar lavage (BAL) and type II pneumocytes were determined.Lipid peroxidation (LPO) was also measured in type II cells. To investigate the basis of these observations,GSH metabolism in type II pneumocytes was studied, analyzing mRNA expression of g-glutamylcystein synthetase(gamma-GCS), glutathione synthetase (GS), gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidases(GPXs) and glutathione reductase (GR). Furthermore, enzyme activities of GPX and GR were determined.Results: In acute and chronic lung injury the GSH/GSSG ratio was reduced in blood and BAL, but therewas no change in type II pneumocytes. LPO in type II cells was only reduced in acute lung injury. Inboth kinds of lung injury mRNA expression of gamma-GCS, GS and GPX3 decreased, while expression of gamma-GTand GR increased. GPX4 mRNA expression decreased in acute lung injury and increased in the chronic state.Enzyme activity of GPX and GR was generally increased in lung injury. Conclusions: In NO(2) induced acuteand chronic lung injury, GSH metabolism is imbalanced.

Keywords: Acute Disease, Animals, Chronic Disease, Enzymes - genetics, Glutathione - biosynthesis, Glutathione - metabolism, Glutathione Peroxidase - metabolism, Lung - drug effects, Lung - injuries, Lung - metabolism, Lung - pathology, Nitrogen Dioxide - toxicity, Oxidation-Reduction - drug effects, Oxidative Stress - drug effects, RNA, Messenger - genetics, RNA, Messenger - metabolism, Rats, Acute Disease, Animals, Chronic Disease, Enzymes - genetics, Glutathione - metabolism, Glutathione Peroxidase - metabolism, Lung - pathology, Lung Injury, Nitrogen Dioxide - toxicity, Oxidation-Reduction - drug effects, Oxidative Stress - drug effects, RNA, Messenger - metabolism, Rats