, Volume 164, Issue 1, pp 93–106 | Cite as

Mechanism of oxygen toxicity in rat lungs

  • Masaru Iwata
  • Kenzo Takagi
  • Tatsuo Satake
  • Satoru Sugiyama
  • Takayuki Ozawa


This study was designed to investigate the mechanism responsible for lung injury in rats induced by oxygen breathing. After oxygen exposure for 60 h the rats began to die, and mortality reached 85% after 72 h of exposure. After 48 h and 60 h of oxygen exposure, the microsomal lipid peroxide (LPO) level was increased significantly compared to control rats. The microsomal ATP-dependent calcium uptake was decreased significantly after 48 h and 60 h of oxygen exposure when compared with the control. The endogenous phospholipase activity in lung membrane fractions was elevated significantly after 48 h and 60 h of oxygen exposure, respectively. After 48 h and 60 h of oxygen exposure, leukotriene B4 (LTB4) level in lung lavages was also increased significantly compared with the control. The number of polymorphonuclear leukocytes (PMN) in lavages was increased significantly after 60 h of oxygen exposure. Administration of verapamil prevented the elevation of the phospholipase activity, LTB4 level and the number of PMN, and reduced the mortality rate to 40% at 72 h, while it did not affect the formation of LPO or the depression of the calcium uptake. Calcium is the essential activator of phospholipase. Therefore, decreased calcium uptake in lung microsomes is considered to induce disturbance in intracellular calcium regulation, which, in turn, causes the activation of phospholipase, resulting in the elevation of LTB4, a potent chemotactic agent for PMN. Verapamil could prevent the disturbance of intracellular calcium regulation by inhibiting calcium influx and the activation of phospholipase. The enhanced phospholipase activity and associated elevation of lipoxygenase product are responsible for lung damage induced by pure oxygen breathing.

Key words

Oxygen toxicity Lipid peroxides Calcium uptake Phospholipase Leukotriene B4 


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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Masaru Iwata
    • 1
  • Kenzo Takagi
    • 1
  • Tatsuo Satake
    • 1
  • Satoru Sugiyama
    • 2
  • Takayuki Ozawa
    • 2
  1. 1.Departments of Internal MedicineUniversity of NagoyaNagoyaJapan
  2. 2.Biomedical Chemistry, Faculty of MedicineUniversity of NagoyaNagoyaJapan

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