Adaptation to multiday ozone exposure is associated with a sustained increase of bronchoalveolar uric acid

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 ppm ozone, 12 h day(-1) for seven consecutive days. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed before, after the first (D1), third (D3) and seventh (D7) exposure. Differential cell count, total proteins, 8-epi-PGF2alpha, 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 D1. By repeating ozone exposures, progressive functional adaptation occurred. Ozone induced a significant increase of BAL neutrophil percentage on D1. On D3 and D7, neutrophil percentage was progressively decreased, but remained significantly elevated. BAL total proteins were significantly increased on D1 and decreased progressively until D7. 8-Epi-PGF2alpha was significantly increased on D1 and was returned to baseline on D3 and D7, whilst glutathione significantly increased on D3 and returned to baseline on D7. Uric acid was increased ten-fold on D1. On D3, uric acid was increased six-fold and was persistently elevated at D7. This study suggests that ozone adaptation of functional and inflammatory variables is accompanied with sustained BAL uric acid elevation.