Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation.

In vitro studies suggest that reactive oxygen species contribute to the cardiopulmonary toxicity of particulate air pollution. To evaluate the ability of particulate air pollution to promote oxidative stress and tissue damage in vivo, we studied a rat model of short-term exposure to concentrated ambient particles (CAPs). We exposed adult Sprague-Dawley rats to either CAPs aerosols (group 1; average CAPs mass concentration, 300 +/- 60 micro g/m3) or filtered air (sham controls) for periods of 1-5 hr. Rats breathing CAPs aerosols for 5 hr showed significant oxidative stress, determined as in situ chemiluminescence in the lung [group 1, 41 +/- 4; sham, 24 +/- 1 counts per second (cps)/cm2] and heart (group 1, 45 +/- 4; sham, 24 +/- 2 cps/cm2) but not liver (group 1, 10 +/- 3; sham, 13 +/- 3 cps/cm2). Increases in oxidant levels were also triggered by highly toxic residual oil fly ash particles (lung chemiluminescence, 90 +/- 10 cps/cm2; heart chemiluminescence, 50 +/- 3 cps/cm2) but not by particle-free air or by inert carbon black aerosols (control particles). Increases in chemiluminescence showed strong associations with the CAPs content of iron, manganese, copper, and zinc in the lung and with Fe, aluminum, silicon, and titanium in the heart. The oxidant stress imposed by 5-hr exposure to CAPs was associated with slight but significant increases in the lung and heart water content (approximately 5% in both tissues, p < 0.05) and with increased serum levels of lactate dehydrogenase (approximately 80%), indicating mild damage to both tissues. Strikingly, CAPs inhalation also led to tissue-specific increases in the activities of the antioxidant enzymes superoxide dismutase and catalase, suggesting that episodes of increased particulate air pollution not only have potential for oxidant injurious effects but may also trigger adaptive responses.

[1]  B. Halliwell,et al.  Role of free radicals and catalytic metal ions in human disease: an overview. , 1990, Methods in enzymology.

[2]  Division on Earth Guide for the Care and Use of Laboratory Animals , 1996 .

[3]  C. Monn,et al.  Cytotoxicity and induction of proinflammatory cytokines from human monocytes exposed to fine (PM2.5) and coarse particles (PM10-2.5) in outdoor and indoor air. , 1999, Toxicology and applied pharmacology.

[4]  E. Cadenas,et al.  Low-level chemiluminescence as an indicator of singlet molecular oxygen in biological systems. , 1984, Methods in enzymology.

[5]  P. Catalano,et al.  Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines. , 2000, Environmental health perspectives.

[6]  P. Koutrakis,et al.  A technique to expose animals to concentrated fine ambient aerosols. , 1995, Environmental health perspectives.

[7]  P. Catalano,et al.  INFLAMMATION, CHEMOKINE EXPRESSION, AND DEATH IN MONOCROTALINE-TREATED RATS FOLLOWING FUEL OIL FLY ASH INHALATION , 1997 .

[8]  P. Catalano,et al.  Age-Related Responses in Rats to Concentrated Urban Air Particles (CAPs) , 2000 .

[9]  S. Llesuy,et al.  Oxidative stress in mouse heart by antitumoral drugs: a comparative study of doxorubicin and mitoxantrone. , 1993, Toxicology.

[10]  A. Nel,et al.  The role of particulate pollutants in pulmonary inflammation and asthma: evidence for the involvement of organic chemicals and oxidative stress , 2001, Current opinion in pulmonary medicine.

[11]  D. Crawford Regulation of Mammalian Gene Expression by Reactive Oxygen Species , 2002 .

[12]  M. Schladweiler,et al.  A pulmonary rat gene array for screening altered expression profiles in air pollutant-induced lung injury. , 2000, Inhalation toxicology.

[13]  C. Giulivi,et al.  Spontaneous lung chemiluminescence upon paraquat administration. , 1988, Free radical biology & medicine.

[14]  E. Racker Spectrophotometric measurements of the enzymatic formation of fumaric and cis-aconitic acids. , 1950, Biochimica et biophysica acta.

[15]  C. Koop Report of the Surgeon General's Workshop on Organ Procurement: Liver Transplantation--NIH Consensus Development Conference at the National Institutes of Health, Bethesda, MD , 1983 .

[16]  J. R. Koehler,et al.  Modern Applied Statistics with S-Plus. , 1996 .

[17]  A. Imrich,et al.  Analysis of air pollution particulate-mediated oxidant stress in alveolar macrophages. , 1998, Journal of toxicology and environmental health. Part A.

[18]  J. Kaiser Evidence Mounts That Tiny Particles Can Kill , 2000, Science.

[19]  C. J. Chung,et al.  Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  H. Nick,et al.  Inflammatory Regulation of Manganese Superoxide Dismutase , 2002 .

[21]  M. Schroeter,et al.  Effects of oxidative stress on the expression of antioxidative defense enzymes in spontaneously hypertensive rat hearts. , 2000, Free radical biology & medicine.

[22]  Xiao-ling Guo,et al.  Effect of oxygen on lung superoxide dismutase activities in premature baboons with bronchopulmonary dysplasia. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[23]  P. Vacek,et al.  Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. , 2000, American journal of respiratory cell and molecular biology.

[24]  J. Turrens,et al.  Activated polymorphonuclear leukocytes increase low-level chemiluminescence of isolated perfused rat lungs. , 1993, Journal of applied physiology.

[25]  D. Massaro,et al.  Tolerance of rats to hyperoxia. Lung antioxidant enzyme gene expression. , 1993, The Journal of clinical investigation.

[26]  C. Giulivi,et al.  METABOLIC REGULATION IN OXIDATIVE STRESS: AN OVERVIEW. , 1991 .

[27]  A. Imrich,et al.  Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles. , 1999, Toxicology and applied pharmacology.

[28]  P. Evelson,et al.  Time course and quantitative analysis of the adaptive responses to 85% oxygen in the rat lung and heart. , 2000, Biochimica et biophysica acta.

[29]  B. Mossman,et al.  MECHANISMS OF ACTION OF POORLY SOLUBLE PARTICULATES IN OVERLOAD-RELATED LUNG PATHOLOGY , 2000, Inhalation toxicology.

[30]  W. MacNee,et al.  Activation of NF-κB by PM10 Occurs via an Iron-Mediated Mechanism in the Absence of IκB Degradation , 2000 .

[31]  D. Costa,et al.  In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. , 1997, Chemical research in toxicology.

[32]  M. Madden,et al.  Acetaldehyde (CH3CHO) production in rodent lung after exposure to metal-rich particles. , 1999, Free radical biology & medicine.

[33]  Dennis P. Nelson,et al.  Enthalpy of Decomposition of Hydrogen Peroxide by Catalase at 25C (with Molar Extinction Coefficients of H2O2 Solutions in the UV) , 1972 .

[34]  I. Fridovich,et al.  Isozymes of superoxide dismutase from wheat germ. , 1973, Biochimica et biophysica acta.

[35]  E R James,et al.  Superoxide dismutase. , 1994, Parasitology today.

[36]  J. Crapo,et al.  Oxygen-induced changes in pulmonary superoxide dismutase assayed by antibody titrations. , 1976, The American journal of physiology.

[37]  R. Devlin,et al.  Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. , 2000, American journal of respiratory and critical care medicine.

[38]  F. Pooley,et al.  The response of lung epithelium to well characterised fine particles. , 1998, Life sciences.

[39]  J M Wolfson,et al.  Mechanisms of morbidity and mortality from exposure to ambient air particles. , 2000, Research report.

[40]  K. Pinkerton,et al.  Dose-dependent tolerance to ozone. IV. Site-specific elevation in antioxidant enzymes in the lungs of rats exposed for 90 days or 20 months. , 1994, Toxicology and applied pharmacology.

[41]  S. Boland,et al.  Airborne particles evoke an inflammatory response in human airway epithelium. Activation of transcription factors , 2004, Cell Biology and Toxicology.

[42]  A. Boveris,et al.  Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. , 1993, The Journal of clinical investigation.

[43]  A. Churg,et al.  Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells. , 1998, Cancer research.

[44]  D P Nelson,et al.  Enthalpy of decomposition of hydrogen peroxide by catalase at 25 degrees C (with molar extinction coefficients of H 2 O 2 solutions in the UV). , 1972, Analytical biochemistry.

[45]  A. Churg,et al.  Mechanisms of mineral dust-induced emphysema. , 1997, Environmental health perspectives.

[46]  G. Schmuck,et al.  Changes in antioxidant enzyme expression in response to hydrogen peroxide in rat astroglial cells , 2001, Archives of Toxicology.

[47]  R. Devlin,et al.  Canines as sentinel species for assessing chronic exposures to air pollutants: part 2. Cardiac pathology. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[48]  B Chance,et al.  Organ chemiluminescence: noninvasive assay for oxidative radical reactions. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[49]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.

[50]  L. Kobzik,et al.  Environmental particulate-mediated cytokine production in lung epithelial cells (A549): role of preexisting inflammation and oxidant stress. , 1998, Journal of toxicology and environmental health. Part A.

[51]  H. Nick,et al.  Regulation of superoxide dismutase in primary cultures of rat colonic smooth muscle cells. , 1997, The American journal of physiology.

[52]  Acute lung injury from intratracheal exposure to fugitive residual oil fly ash and its constituent metals in normo- and spontaneously hypertensive rats. , 2001, Inhalation toxicology.

[53]  J Inmon,et al.  Ambient air particles: effects on cellular oxidant radical generation in relation to particulate elemental chemistry. , 1999, Toxicology and applied pharmacology.

[54]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.