Adaptation to Multiday Ozone Exposure is Associated with a Sustained Increase of Bronchoalveolar Uric Acid

Abstract

The phenomenon of ozone tolerance is described, but the underlying mechanisms remain unknown. We tested whether adaptation to multiday ozone exposure was related to an upregulated pulmonary antioxidant defence. Six calves were exposed to 0.75 u ppm ozone, 12 u h u day m 1 for seven consecutive days. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed before, after the first (D 1 ), third (D 3 ) and seventh (D 7 ) exposure. Differential cell count, total proteins, 8-epi-PGF 2 f , glutathione and uric acid were determined in BAL. Dynamic lung compliance and arterial oxygen tension were significantly decreased and lung oedema impaired pulmonary function on D 1 . By repeating ozone exposures, progressive functional adaptation occurred. Ozone induced a significant increase of BAL neutrophil percentage on D 1 . On D 3 and D 7 , neutrophil percentage was progressively decreased, but remained significantly elevated. BAL total proteins were significantly increased on D 1 and decreased progressively until D 7 . 8-Epi-PGF 2 f was significantly increased on D 1 and was returned to baseline on D 3 and D 7 , whilst glutathione significantly increased on D 3 and returned to baseline on D 7 . Uric acid was increased ten-fold on D 1 . On D 3 , uric acid was increased six-fold and was persistently elevated at D 7 . This study suggests that ozone adaptation of functional and inflammatory variables is accompanied with sustained BAL uric acid elevation.