Skip to main content
SpringerLink
Log in

Mechanisms of pulmonary oxygen toxicity

  • Review
  • Published:
Lung Aims and scope Submit manuscript

Abstract

Increasing use of oxygen in clinical practice has provided new impetus for determining mechanisms of acute pulmonary oxygen toxicity. The pathophysiology of lungs exposed to oxygen in vivo and in vitro suggests a direct toxic effect of hyperoxia upon lung cells, with variation in sensitivity to injury among cell types. The currently accepted primary mechanism for oxygen-induced cellular injury is enhanced oxygen-derived free radical generation with subsequent oxidative attack upon basic cell constituents. The major intracellular sources of increased free radicals are undetermined, but there is sufficient evidence that the extracellular contribution, specifically from PMN leukocyte influx into lungs is not critical to lethal pulmonary oxygen toxicity. Cellular protection is provided by intracellular enzymatic and nonenzymatic anti-oxidant defenses, which can be manipulated by experimental treatments to alter survival in O2. Our increasing knowledge of the mechanisms of oxidant toxicity may lead to improved strategies for early detection of lung damage and for the prevention or treatment of injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Article Open access 19 December 2021

Mervyn Singer, Paul J. Young, … Peter Radermacher

References

  1. Bean JW (1945) Effects of oxygen at increased pressure. Physiol Rev 25:1–147

    CAS  Google Scholar 

  2. Berg JT, Smith RM (1984) Endotoxin protection of rats from O2 toxicity: chemiluminescence of lung neutrophils. Res Commun Chem Pathol Pharmacol 44:461–476

    PubMed  CAS  Google Scholar 

  3. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605

    PubMed  CAS  Google Scholar 

  4. Crapo JD, Barry BE, Foscue HA, Shelburne J (1980) Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am Rev Respir Dis 122:123–143

    PubMed  CAS  Google Scholar 

  5. Fisher AB (1980) Oxygen therapy. Am Rev Respir Dis 122:61–69

    PubMed  CAS  Google Scholar 

  6. Fisher AB, Bassett DJP, Forman HJ (1979) Oxygen toxicity of the lung: biochemical aspects. In: Fishman A, Renkin E (eds) Pulmonary edema. American Physiological Society, Bestheda, Md, 1979, pp 207–216

    Google Scholar 

  7. Fisher AB, Diamond S, Mellen S (1974) Effect of O2 exposure on metabolism of the rabbit alveolar macrophage. J Appl Physiol 37:341–345

    PubMed  Google Scholar 

  8. Forman HJ, Fisher AB (1981) Antioxidant defenses. In: Gilbert DL (ed) Oxygen and living processes. Springer, New York Heidelberg Berlin, pp 235–249

    Google Scholar 

  9. Forman HJ, Williams JJ, Nelson J, Daniele RP, Fisher AB (1982) Hyperoxia inhibits stimulated superoxide release by rat alveolar macrophages. J Appl Physiol 53:685–689

    PubMed  CAS  Google Scholar 

  10. Fox RB, Hoidal JR, Brown DM, Repine JE (1981) Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes. Am Rev Respir Dis 123:521–523

    PubMed  CAS  Google Scholar 

  11. Frank L, Summerville J, Massaro D (1980) Protection from oxygen toxicity with endotoxin. J Clin Invest 65:1104–1110

    PubMed  CAS  Google Scholar 

  12. Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256:10986–10992

    PubMed  CAS  Google Scholar 

  13. Freeman A, Crapo JD (1982) Free radicals and tissue injury. Lab Invest 47:412–426

    PubMed  CAS  Google Scholar 

  14. Fridovich I (1981) Superoxide radical and superoxide dismutase. In: Gilbert DL (ed) Oxygen and living processes. Springer, New York Heidelberg Berlin, pp 250–272

    Google Scholar 

  15. Gerschman R (1964) Biological effects of oxygen. In: Dickens EF, Neil E (eds) Oxygen in the animal organism. Macmillan, New York, pp 475–494

    Google Scholar 

  16. Glass M, Forman HJ, Rotman EI, Clark JM, Pietra GG, Fisher AB (1985) Cellular composition of lung lavage in oxygen toxicity. Fed Proc (abstr) (in press)

  17. Huber GL, Drath DB (1981) Pulmonary oxygen toxicity. In: Gilbert DL (ed) Oxygen and living processes. Springer, New York, pp 273–342

    Google Scholar 

  18. Johnson KJ, Fantone JC, Kaplan J, Ward PA (1981) In vivo damage of rat lungs by oxygen metabolites. J Clin Invest 67:983–993

    PubMed  CAS  Google Scholar 

  19. Kapanci Y, Weibel ER, Kaplan HP, Robinson FR (1969) Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. II. Ultrastructural and morphometric studies. Lab Invest 20:101–118

    PubMed  CAS  Google Scholar 

  20. Lorrain-Smith J (1899) The pathological effects due to increase of oxygen tension in the air breathed. J Physiol 24:19–25

    Google Scholar 

  21. Martin WJ, Gadek JE, Hunninghake GW, Crystal RG (1981) Oxidant injury of lung parenchymal cells. J Clin Invest 68:1277–1288

    PubMed  CAS  Google Scholar 

  22. Ohlsson WTI (1947) A study on oxygen at atmospheric pressure. Acta Med Scand [Suppl] 190:1–93

    Google Scholar 

  23. Raj JU, Bland RD (1983) Neutrophil depletion does not prevent oxygen-induced lung injury in rabbits. Chest 83:20s-21s

    PubMed  CAS  Google Scholar 

  24. Rister M, Baehner RL (1977) Effect of hyperoxia on superoxide anion and hydrogen peroxide production of polymorphonuclear leucocytes and alveolar macrophages. Br J Haematol 36:241–248

    PubMed  CAS  Google Scholar 

  25. Shasby DM, Fox RB, Harada RN, Repine JE (1982) Reduction of the edema of acute hyperoxic lung injury by granulocyte depletion. J Appl Physiol 52:1237–1244

    PubMed  CAS  Google Scholar 

  26. Smith B, Winter PM, Wheelis RF (1973) Increased normobaric oxygen tolerance of rabbits following oleic acid-induced lung damage. J Appl Physiol 35:395–400

    PubMed  CAS  Google Scholar 

  27. Steinberg H, Greenwald RA, Sciubba J, Das DK (1982) The effect of oxygen-derived free radicals on pulmonary endothelial cell function in the isolated perfused rat lung. Exp Lung Res 3:163–173

    PubMed  CAS  Google Scholar 

  28. Suttorp N, Simon LM (1982) Lung cell oxidant injury. Enhancement of polymorphonuclear leukocyte-mediated cytotoxicity in lung cells exposed to sustained in vitro hyperoxia. J Clin Invest 70:342–350

    Article  PubMed  CAS  Google Scholar 

  29. Thet LA, Wrobel DJ, Crapo JD, Shelburne JD (1983) Morphologic aspects of the protection by endotoxin against acute and chronic oxygen-induced lung injury in adult rats. Lab Invest 48:448–457

    PubMed  CAS  Google Scholar 

  30. Tierney DF, Ayers L, Lasuyama RS (1977) Altered sensitivity to oxygen toxicity. Am Rev Respir Dis 115:59–65

    PubMed  CAS  Google Scholar 

  31. Turrens JF, Freeman BA, Crapo JD (1982) Hyperoxia increases H2O2 release by lung mitochondria and microsomes. Arch Biochem Biophys 217:411–421

    Article  PubMed  CAS  Google Scholar 

  32. Yusa T, Crapo JD, Freeman BA (1984) Hyperoxia enhances lung and liver nuclear superoxide generation. Biochim Biophys Acta 798:167–174

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Pennsylvania School of Medicine, 37th and Hamilton Walk, D-404 Richards Building, G/4, 19104, Philadelphia, Pennsylvania, USA

    Aron B. Fisher, Henry J. Forman & Mitchell Glass

Authors
  1. Aron B. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry J. Forman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitchell Glass
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fisher, A.B., Forman, H.J. & Glass, M. Mechanisms of pulmonary oxygen toxicity. Lung 162, 255–259 (1984). https://doi.org/10.1007/BF02715655

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02715655

Key words

Search

Navigation