MODELING THE INTERACTIONS OF OZONE WITH PULMONARY EPITHELIAL LINING FLUID ANTIOXIDANTS

Water soluble antioxidant-ascorbate (AA), urate (UA), and reduced glut athione (GSH)-consumption by ozone (O-3) was investigated in a range o f pulmonary epithelial lining fluid (ELF) models. Antioxidants were ex posed individually and as a composite mixture, with and without human albumin to a range of ambient O-3 concentrations: 0-1500 ppb using a c ontinually mixed, interfacial exposure setup, We observed the followin g: (1) UA constituted the most O-3-reactive substrate in each of the m odels examined. Reactivity hierarchies in each were as follows: UA > A A much greater than GSH (individual antioxidant), UA > AA > GSH (compo site antioxidant), and UA much greater than AA approximate to GSH (com posite antioxidant + albumin). (2) Consumption of GSH as a pure antiox idant solution was associated with a 2:1 stoichiometric conversion of GSH to GSSG. This simplistic relationship was lost in the more complex models. (3) Consumption of antioxidants by O-3 occurred without alter ation of sample pH. (4) Protein carbonyl formation was observed when a lbumin alone was exposed to O-3. However, in the presence of the compo site antioxidant solution no evidence of this oxidative modification w as apparent. These data indicate that GSH does not represent an import ant substrate for O-3. In contrast, UA displays high reactivity consis tent with its acting as a sacrificial substrate in the ELF. As UA conc entrations are highest in the ELF of the proximal airways, its localiz ation, allied to its reactivity, suggests that it plays important role s, both in conferring protection locally and also by ''scrubbing'' O-3 from inhaled air, limiting its penetration to the more sensitive dist al lung. (C) 1998 Academic Press.