title: Antioxidant-mediated augmentation of ozone-induced membrane oxidation.
abstract: The pulmonary epithelial lining fluid (ELF) contains substrates, e.g., ascorbic acid (AH2), uric acid (UA), glutathione (GSH), proteins, and unsaturated lipids, which undergo facile reaction with inhaled ozone (O3). Reactions near the ELF gas/liquid interface likely provide the driving force for O3 absorption ("reactive absorption") and constrain O3 diffusion to the underlying epithelium. To investigate the potential mechanisms wherein O3/ELF interactions may induce cellular damage, we utilized a red cell membrane (RCM) model intermittently covered by an aqueous film to mimic the lung surface compartmentation, and evaluated exposure-mediated loss of acetylcholinesterase activity (AChE) and TBARS accumulation. In the absence of aqueous reactants, O3 exposure induced no detectable changes in AChE or TBARS. AH2 and GSH preferentially induced oxidative damage in a dose-dependent fashion. AH2-mediated RCM oxidation was not inhibited by superoxide dismutase, catalase, mannitol, or Fe chelators. O3 reaction with UA, Trolox, or albumin produced no RCM oxidation but oxidation occurred when AH2 was combined with UA or albumin. Rat bronchoalveolar lavage fluid (BALF) also induced RCM oxidation. However, in vivo O3 exposure dampened the extent of BALF-mediated RCM oxidation. Although we cannot completely rule out O3 diffusion to the RCM, product(s) derived from O3 + AH2/GSH reactions (possibly O3*- or 1O2) likely initiated RCM oxidation and may suggest that in vivo, such secondary species account for O3 permeation through the ELF leading to cellular perturbations.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, RBPH 530, 1530 3rd Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Ballinger
authors.forename: Rafael
authors.initials: R
authors.lastname: Cueto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Squadrito
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Coffin
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Velsor
authors.forename: William A
authors.initials: WA
authors.lastname: Pryor
authors.forename: Edward M
authors.initials: EM
authors.lastname: Postlethwait
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D002839:Chromans / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D010126:Ozone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D002839:Chromans; D014527:Uric Acid; D010126:Ozone; D007770:L-Lactate Dehydrogenase; D000110:Acetylcholinesterase; D005978:Glutathione; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid