Modeling the interactions of ozone with pulmonary epithelial lining fluid antioxidants

被引:43
作者
Mudway, IS [1 ]
Kelly, FJ [1 ]
机构
[1] St Thomas Hosp, Rayne Inst, London SE1 7EH, England
基金
英国惠康基金;
关键词
D O I
10.1006/taap.1997.8318
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Water soluble antioxidant-ascorbate (AA), urate (UA), and reduced glutathione (GSH)-consumption by ozone (O-3) was investigated in a range of pulmonary epithelial lining fluid (ELF) models. Antioxidants were exposed individually and as a composite mixture, with and without human albumin to a range of ambient O-3 concentrations: 0-1500 ppb using a continually mixed, interfacial exposure setup, We observed the following: (1) UA constituted the most O-3-reactive substrate in each of the models examined. Reactivity hierarchies in each were as follows: UA > AA much greater than GSH (individual antioxidant), UA > AA > GSH (composite antioxidant), and UA much greater than AA approximate to GSH (composite antioxidant + albumin). (2) Consumption of GSH as a pure antioxidant 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 alteration of sample pH. (4) Protein carbonyl formation was observed when albumin alone was exposed to O-3. However, in the presence of the composite antioxidant solution no evidence of this oxidative modification was apparent. These data indicate that GSH does not represent an important substrate for O-3. In contrast, UA displays high reactivity consistent with its acting as a sacrificial substrate in the ELF. As UA concentrations are highest in the ELF of the proximal airways, its localization, allied to its reactivity, suggests that it plays important roles, both in conferring protection locally and also by "scrubbing" O-3 from inhaled air, limiting its penetration to the more sensitive distal lung. (C) 1998 Academic Press.
引用
收藏
页码:91 / 100
页数:10
相关论文
共 47 条
  • [1] MICROTITER PLATE ASSAY FOR THE MEASUREMENT OF GLUTATHIONE AND GLUTATHIONE DISULFIDE IN LARGE NUMBERS OF BIOLOGICAL SAMPLES
    BAKER, MA
    CERNIGLIA, GJ
    ZAMAN, A
    [J]. ANALYTICAL BIOCHEMISTRY, 1990, 190 (02) : 360 - 365
  • [2] BARTLETT WS, 1995, J BIOL CHEM, V271, P4177
  • [3] BECKETT WS, 1991, YALE J BIOL MED, V64, P167
  • [4] 0.35 PPM O-3 EXPOSURE INDUCES HYPERRESPONSIVENESS ON 24-H REEXPOSURE TO 0.20 PPM O-3
    BROOKES, KA
    ADAMS, WC
    SCHELEGLE, ES
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (06) : 2756 - 2762
  • [5] NORMAL ALVEOLAR EPITHELIAL LINING FLUID CONTAINS HIGH-LEVELS OF GLUTATHIONE
    CANTIN, AM
    NORTH, SL
    HUBBARD, RC
    CRYSTAL, RG
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1987, 63 (01) : 152 - 157
  • [6] OXIDATIVE DAMAGE TO PLASMA CONSTITUENTS BY OZONE
    CROSS, CE
    MOTCHNIK, PA
    BRUENER, BA
    JONES, DA
    KAUR, H
    AMES, BN
    HALLIWELL, B
    [J]. FEBS LETTERS, 1992, 298 (2-3) : 269 - 272
  • [7] OXIDATIVE DAMAGE TO HUMAN PLASMA-PROTEINS BY OZONE
    CROSS, CE
    REZNICK, AZ
    PACKER, L
    DAVIS, PA
    SUZUKI, YJ
    HALLIWELL, B
    [J]. FREE RADICAL RESEARCH COMMUNICATIONS, 1992, 15 (06): : 347 - 352
  • [8] PULMONARY-FUNCTION AND SYMPTOM RESPONSES AFTER 6.6-HOUR EXPOSURE TO 0.12 PPM OZONE WITH MODERATE EXERCISE
    FOLINSBEE, LJ
    MCDONNELL, WF
    HORSTMAN, DH
    [J]. JAPCA-THE INTERNATIONAL JOURNAL OF AIR POLLUTION CONTROL AND HAZARDOUS WASTE MANAGEMENT, 1988, 38 (01): : 28 - 35
  • [9] A COMPARISON OF THE RATES OF OZONATION OF BIOLOGICAL ANTIOXIDANTS AND OLEATE AND LINOLEATE ESTERS
    GIAMALVA, D
    CHURCH, DF
    PRYOR, WA
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 133 (02) : 773 - 779
  • [10] REACTION-PRODUCTS OF OZONE - A REVIEW
    GLAZE, WH
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1986, 69 : 151 - 157