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. 2002 Aug;110(8):749–755. doi: 10.1289/ehp.02110749

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

Sonia A Gurgueira 1, Joy Lawrence 1, Brent Coull 1, G G Krishna Murthy 1, Beatriz González-Flecha 1
PMCID: PMC1240944  PMID: 12153754

Abstract

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.

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Selected References

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  1. Baeza-Squiban A., Bonvallot V., Boland S., Marano F. Airborne particles evoke an inflammatory response in human airway epithelium. Activation of transcription factors. Cell Biol Toxicol. 1999;15(6):375–380. doi: 10.1023/a:1007653900063. [DOI] [PubMed] [Google Scholar]
  2. Barnard M. L., Gurdian S., Turrens J. F. Activated polymorphonuclear leukocytes increase low-level chemiluminescence of isolated perfused rat lungs. J Appl Physiol (1985) 1993 Aug;75(2):933–939. doi: 10.1152/jappl.1993.75.2.933. [DOI] [PubMed] [Google Scholar]
  3. Beauchamp C. O., Fridovich I. Isozymes of superoxide dismutase from wheat germ. Biochim Biophys Acta. 1973 Jul 12;317(1):50–64. doi: 10.1016/0005-2795(73)90198-0. [DOI] [PubMed] [Google Scholar]
  4. Boveris A., Cadenas E., Reiter R., Filipkowski M., Nakase Y., Chance B. Organ chemiluminescence: noninvasive assay for oxidative radical reactions. Proc Natl Acad Sci U S A. 1980 Jan;77(1):347–351. doi: 10.1073/pnas.77.1.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cadenas E., Sies H. Low-level chemiluminescence as an indicator of singlet molecular oxygen in biological systems. Methods Enzymol. 1984;105:221–231. doi: 10.1016/s0076-6879(84)05029-1. [DOI] [PubMed] [Google Scholar]
  6. Calderón-Garcidueñas L., Mora-Tiscareño A., Fordham L. A., Chung C. J., García R., Osnaya N., Hernández J., Acuña H., Gambling T. M., Villarreal-Calderón A. Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology. Toxicol Sci. 2001 Jun;61(2):342–355. doi: 10.1093/toxsci/61.2.342. [DOI] [PubMed] [Google Scholar]
  7. Churg A., Zay K., Li K. Mechanisms of mineral dust-induced emphysema. Environ Health Perspect. 1997 Sep;105 (Suppl 5):1215–1218. doi: 10.1289/ehp.97105s51215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clarke R. W., Coull B., Reinisch U., Catalano P., Killingsworth C. R., Koutrakis P., Kavouras I., Murthy G. G., Lawrence J., Lovett E. Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines. Environ Health Perspect. 2000 Dec;108(12):1179–1187. doi: 10.1289/ehp.001081179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clerch L. B., Massaro D. Tolerance of rats to hyperoxia. Lung antioxidant enzyme gene expression. J Clin Invest. 1993 Feb;91(2):499–508. doi: 10.1172/JCI116228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crapo J. D., McCord J. M. Oxygen-induced changes in pulmonary superoxide dismutase assayed by antibody titrations. Am J Physiol. 1976 Oct;231(4):1196–1203. doi: 10.1152/ajplegacy.1976.231.4.1196. [DOI] [PubMed] [Google Scholar]
  11. Csonka C., Pataki T., Kovacs P., Müller S. L., Schroeter M. L., Tosaki A., Blasig I. E. Effects of oxidative stress on the expression of antioxidative defense enzymes in spontaneously hypertensive rat hearts. Free Radic Biol Med. 2000 Oct 1;29(7):612–619. doi: 10.1016/s0891-5849(00)00365-8. [DOI] [PubMed] [Google Scholar]
  12. Evelson P., González-Flecha B. Time course and quantitative analysis of the adaptive responses to 85% oxygen in the rat lung and heart. Biochim Biophys Acta. 2000 Oct 18;1523(2-3):209–216. doi: 10.1016/s0304-4165(00)00124-0. [DOI] [PubMed] [Google Scholar]
  13. Ghio A. J., Kim C., Devlin R. B. Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):981–988. doi: 10.1164/ajrccm.162.3.9911115. [DOI] [PubMed] [Google Scholar]
  14. Goldsmith C. A., Imrich A., Danaee H., Ning Y. Y., Kobzik L. Analysis of air pollution particulate-mediated oxidant stress in alveolar macrophages. J Toxicol Environ Health A. 1998 Aug 7;54(7):529–545. doi: 10.1080/009841098158683. [DOI] [PubMed] [Google Scholar]
  15. González-Flecha B., Cutrin J. C., Boveris A. Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest. 1993 Feb;91(2):456–464. doi: 10.1172/JCI116223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Halliwell B., Gutteridge J. M. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 1990;186:1–85. doi: 10.1016/0076-6879(90)86093-b. [DOI] [PubMed] [Google Scholar]
  17. Imrich A., Ning Y. Y., Koziel H., Coull B., Kobzik L. Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles. Toxicol Appl Pharmacol. 1999 Sep 1;159(2):117–124. doi: 10.1006/taap.1999.8731. [DOI] [PubMed] [Google Scholar]
  18. Jiménez L. A., Thompson J., Brown D. A., Rahman I., Antonicelli F., Duffin R., Drost E. M., Hay R. T., Donaldson K., MacNee W. Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation. Toxicol Appl Pharmacol. 2000 Jul 15;166(2):101–110. doi: 10.1006/taap.2000.8957. [DOI] [PubMed] [Google Scholar]
  19. Kadiiska M. B., Mason R. P., Dreher K. L., Costa D. L., Ghio A. J. In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. Chem Res Toxicol. 1997 Oct;10(10):1104–1108. doi: 10.1021/tx970049r. [DOI] [PubMed] [Google Scholar]
  20. Kaiser J. Air pollution. Evidence mounts that tiny particles can kill. Science. 2000 Jul 7;289(5476):22–23. doi: 10.1126/science.289.5476.22. [DOI] [PubMed] [Google Scholar]
  21. Kodavanti U. P., Schladweiler M. C., Richards J. R., Costa D. L. Acute lung injury from intratracheal exposure to fugitive residual oil fly ash and its constituent metals in normo- and spontaneously hypertensive rats. Inhal Toxicol. 2001 Jan;13(1):37–54. doi: 10.1080/089583701459056. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Lores Arnaiz S., Llesuy S. Oxidative stress in mouse heart by antitumoral drugs: a comparative study of doxorubicin and mitoxantrone. Toxicology. 1993 Jan 29;77(1-2):31–38. doi: 10.1016/0300-483x(93)90135-f. [DOI] [PubMed] [Google Scholar]
  24. Madden M. C., Thomas M. J., Ghio A. J. Acetaldehyde (CH3CHO) production in rodent lung after exposure to metal-rich particles. Free Radic Biol Med. 1999 Jun;26(11-12):1569–1577. doi: 10.1016/s0891-5849(99)00027-1. [DOI] [PubMed] [Google Scholar]
  25. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  26. Monn C., Becker S. 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. Toxicol Appl Pharmacol. 1999 Mar 15;155(3):245–252. doi: 10.1006/taap.1998.8591. [DOI] [PubMed] [Google Scholar]
  27. Morton R. L., Das K. C., Guo X. L., Iklé D. N., White C. W. Effect of oxygen on lung superoxide dismutase activities in premature baboons with bronchopulmonary dysplasia. Am J Physiol. 1999 Jan;276(1 Pt 1):L64–L74. doi: 10.1152/ajplung.1999.276.1.L64. [DOI] [PubMed] [Google Scholar]
  28. Mossman B. T. Mechanisms of action of poorly soluble particulates in overload-related lung pathology. Inhal Toxicol. 2000 Jan-Feb;12(1-2):141–148. doi: 10.1080/089583700196572. [DOI] [PubMed] [Google Scholar]
  29. Murphy S. A., BéruBé K. A., Pooley F. D., Richards R. J. The response of lung epithelium to well characterised fine particles. Life Sci. 1998;62(19):1789–1799. doi: 10.1016/s0024-3205(98)00141-6. [DOI] [PubMed] [Google Scholar]
  30. Nadadur S. S., Schladweiler M. C., Kodavanti U. P. A pulmonary rat gene array for screening altered expression profiles in air pollutant-induced lung injury. Inhal Toxicol. 2000 Dec;12(12):1239–1254. doi: 10.1080/08958370050198566. [DOI] [PubMed] [Google Scholar]
  31. Nel A. E., Diaz-Sanchez D., Li N. The role of particulate pollutants in pulmonary inflammation and asthma: evidence for the involvement of organic chemicals and oxidative stress. Curr Opin Pulm Med. 2001 Jan;7(1):20–26. doi: 10.1097/00063198-200101000-00004. [DOI] [PubMed] [Google Scholar]
  32. Nelson D. P., Kiesow L. A. 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). Anal Biochem. 1972 Oct;49(2):474–478. doi: 10.1016/0003-2697(72)90451-4. [DOI] [PubMed] [Google Scholar]
  33. Plopper C. G., Duan X., Buckpitt A. R., Pinkerton K. E. Dose-dependent tolerance to ozone. IV. Site-specific elevation in antioxidant enzymes in the lungs of rats exposed for 90 days or 20 months. Toxicol Appl Pharmacol. 1994 Jul;127(1):124–131. doi: 10.1006/taap.1994.1146. [DOI] [PubMed] [Google Scholar]
  34. Prahalad A. K., Soukup J. M., Inmon J., Willis R., Ghio A. J., Becker S., Gallagher J. E. Ambient air particles: effects on cellular oxidant radical generation in relation to particulate elemental chemistry. Toxicol Appl Pharmacol. 1999 Jul 15;158(2):81–91. doi: 10.1006/taap.1999.8701. [DOI] [PubMed] [Google Scholar]
  35. RACKER E. Spectrophotometric measurements of the enzymatic formation of fumaric and cis-aconitic acids. Biochim Biophys Acta. 1950 Jan;4(1-3):211–214. doi: 10.1016/0006-3002(50)90026-6. [DOI] [PubMed] [Google Scholar]
  36. Rabbee N., Coull B. A., Mehta C., Patel N., Senchaudhuri P. Power and sample size for ordered categorical data. Stat Methods Med Res. 2003 Jan;12(1):73–84. doi: 10.1191/0962280203sm317ra. [DOI] [PubMed] [Google Scholar]
  37. Röhrdanz E., Schmuck G., Ohler S., Tran-Thi Q. H., Kahl R. Changes in antioxidant enzyme expression in response to hydrogen peroxide in rat astroglial cells. Arch Toxicol. 2001 May;75(3):150–158. doi: 10.1007/s002040000206. [DOI] [PubMed] [Google Scholar]
  38. Shukla A., Timblin C., BeruBe K., Gordon T., McKinney W., Driscoll K., Vacek P., Mossman B. T. Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol. 2000 Aug;23(2):182–187. doi: 10.1165/ajrcmb.23.2.4035. [DOI] [PubMed] [Google Scholar]
  39. Sioutas C., Koutrakis P., Burton R. M. A technique to expose animals to concentrated fine ambient aerosols. Environ Health Perspect. 1995 Feb;103(2):172–177. doi: 10.1289/ehp.95103172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stringer B., Kobzik L. Environmental particulate-mediated cytokine production in lung epithelial cells (A549): role of preexisting inflammation and oxidant stress. J Toxicol Environ Health A. 1998 Sep 11;55(1):31–44. doi: 10.1080/009841098158601. [DOI] [PubMed] [Google Scholar]
  41. Tannahill C. L., Stevenot S. A., Eaker E. Y., Sallustio J. E., Nick H. S., Valentine J. F. Regulation of superoxide dismutase in primary cultures of rat colonic smooth muscle cells. Am J Physiol. 1997 May;272(5 Pt 1):G1230–G1235. doi: 10.1152/ajpgi.1997.272.5.G1230. [DOI] [PubMed] [Google Scholar]
  42. Timblin C., BeruBe K., Churg A., Driscoll K., Gordon T., Hemenway D., Walsh E., Cummins A. B., Vacek P., Mossman B. Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells. Cancer Res. 1998 Oct 15;58(20):4543–4547. [PubMed] [Google Scholar]
  43. Turrens J. F., Giulivi C., Pinus C. R., Lavagno C., Boveris A. Spontaneous lung chemiluminescence upon paraquat administration. Free Radic Biol Med. 1988;5(5-6):319–323. doi: 10.1016/0891-5849(88)90103-7. [DOI] [PubMed] [Google Scholar]

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