Effects of ozone and airway inflammation on glutathione status and iron homeostasis in the lungs of horses

OBJECTIVE: To investigate the effects of ozone and airway inflammation on indices of oxidant injury in horses. ANIMALS: 5 clinically normal horses and 25 horses referred for poor performance. PROCEDURE: Blood, tracheal wash, and bronchoalveolar lavage fluid samples were collected before and after ozone exposure (n = 5) or from clinical cases (n = 25), and were analyzed for reduced glutathione (GSH), glutathione disulfide (GSSG), and free and total iron (Fe) values. A scoring system (0 to 5) was used to assess airway inflammation on the basis of clinical signs and cytologic analysis of the tracheal wash and bronchoalveolar lavage fluid samples. RESULTS: Ozone induced significant (P < 0.05) increases in GSH (195.4 +/- 68.5 microM), GSSG (19.4 +/- 6.4 microM), and free (25.5 +/- 16.1 microM) and total (93.1 +/- 13.4 microM) Fe values in the pulmonary epithelial lining fluid, compared with preozone samples (49.2 +/- 18.6, 2.4 +/- 1.2, 0.0, and 33.1 +/- 5.9 microM, respectively). The presence of airway inflammation (19/25) was associated with high GSSG and free and total Fe, but not GSH, values in epithelial lining fluid, compared with values for clinically normal horses (6/25). There were no differences in the systemic values of GSH, GSSG, and free and total Fe between any of the groups. A strong correlation (r = 0.84; P < 0.001) existed between inflammation score and the glutathione redox ratio (GSSG/[GSH + GSSG]) in the 25 horses admitted for clinical examination. CONCLUSIONS: Oxidant injury in the lung will induce changes in the glutathione status and Fe homeostasis that could affect pathogenesis of the disease. CLINICAL RELEVANCE: Measurement of indices of oxidant injury may be useful in the diagnosis of airway inflammation and the response to inhaled oxidants.