Original Contribution ASCORBIC ACID IN NASAL AND TRACHEOBRONCHIAL AIRWAY LINING FLUIDS BETTINA C. S CHOCK, * , y J OHN K OOSTRA, * S UNYE K WACK, * ROBERT M. HACKMAN, z ALBERT VAN DERVLIET, * , § and CARROLL E. CROSS * *Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and Center for Comparative Lung Biology and Medicine, School of Medicine, University of California, Davis, CA, USA; y Department of Medicine, Respiratory Research Group, Queen’s University of Belfa Belfast, Northern Ireland; z Department of Nutrition, University of California, Davis,CA, USA; § Department of Pathology, School of Medicine, University of Vermont, Burlington, VT, USA (Received 18 February 2004; Revised 29 June 2004; Accepted 15 July 2004) Available online 17 August 2004 Abstract—Ascorbic acid (AA) is thought to be an important antioxidant in the respiratory tract, whose regulation to be fully characterized. We investigated whether AA in respiratory tract lining fluids (RTLFs) can be augmented supplementation with AA. Plasma, nasal lavage fluids (NLFs), induced sputum (IS), and saliva were analyzed for AA immediately before and 2 h after ingestion of 2 g of AA in 13 healthy subjects. Concentrations of AA (median an were 52.5 (16.0–88.5), 2.4 (0.18–4.66), 2.4 (0.18–6.00), and 0.55 (0.18–18.90) Amol/l, respectively. Two hours after ingestion of AA, plasma AA increased 2-fold ( p = .004), NLF AA increased 3-fold ( p = .039), but IS and saliva AA not increase. As AA concentrations in saliva and tracheobronchial secretions were low compared with other common extracellular components (such as urate), we evaluated the fate of AA in these fluids. Addition of AA to freshly ob saliva or IS resulted in rapid depletion, which could be largely prevented or reversed by sodium azide or dithioth These findings suggest that oxidant-producing systems in saliva and airway secretions, such as heme peroxidases and other oxidizing substances, rapidly consume AA. Whereas oral supplementation resulted in detectable increases NLFs, its levels in tracheobronchial lining fluid,as measured by IS, were unaffected and remained relatively low, suggesting that AA may play a less significant antioxidant role in this compartment as compared with most other extracellular compartments. D 2004 Elsevier Inc. All rights reserved. Keywords—Ascorbic acid, Uric acid, Nasal fluids, Upper airways, Free radicals INTRODUCTION Respiratory tract lining fluids (RTLFs) represent an important interface between inspired air and respiratory tract cells, and are among the first biological matrices to interact with inhaled environmental oxidants, such as ozone(O 3 ), oxidesof nitrogen (NO x ), and cigarette smoke. RTLFs atthe apical surfaces of repiratory tract epithelial cells also can be expected to interact with oxidantsproduced by activated inflammatory-immune cells present at or recruited to airway surfaces. Thus, although mucin glycoproteins clearly represent a potent tracheobronchial airway antioxidant substance [1], low- molecular-mass antioxidants, such as ascorbic acid (AA) uric acid (UA), and glutathione (GSH), might be expected to modulate respiratory tract susceptibility to environmental oxidantsand activated inflammatory- immune responses occurring at airway surfaces [2–4]. Strong in vitro and in vivo evidence showsthat inhaled O 3 [5–9] and NO 2 [10,11] react rapidly with AA and can decrease AA in complex biological mixtures such as plasma and RTLFs. More recently AA concen- trations in RTLFs have been found to be somewhat reduced in adults with mild asthma [12–14]. However, there is little convincing evidence that supplementation with AA protects against airway hyperreactivity after in vivo exposureto photochemically induced oxidative pollutants (e.g., O 3 and NO 2 ) [15–18]. Although a number of studies appear to suggest a modest effectof large supplements of AA in asthma, a condition that is associated with oxidative stress secon- 1393 Addresscorrespondence to: Caroll E. Cross,M.D., Division of Pulmonary and Critical Care Medicine, University of California, Davis MedicalCenter, 4150 V Street, Suite 3400, Sacramento, CA 95817, USA; Fax: (916) 734 7924; E-mail: cecross@ucdavis.edu. doi:10.1016/j.freeradbiomed.2004.07.023 Free Radical Biology & Medicine, Vol.37,No. 9, pp.1393–1401, 2004 Copyright D 2004 Elsevier Inc. Printed in the USA. All rights reserved 0891-5849/$-see front matter