POTENTIATION OF DIFFUSE LUNG DAMAGE BY OXYGEN - DETERMINING VARIABLES

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Abstract
The antioxidant, butylated hydroxytoluene (BHT) caused diffuse necrosis of type I alveolar cells in mouse lung followed by proliferation of type II epithelial cells. Exposure to O2 during the phase of epithelial cell division led to development of diffuse interstitial fibrosis. Extent of fibrotic changes, as quantitated by measuring total lung hydroxyproline was dependent on O2 concentration in inspired air and length of exposure. Fibrotic changes were seen in animals exposed after 400 mg/kg of BHT for 6 days to 50% O2 or more, 3 days to 60% O2 or more or 2 days to 70% O2 or more but not if exposure was limited to 24 h only. Minimal fibrosis developed in mice exposed for 6 days to 80% O2 alone. Additional factors determining severity of fibrotic changes were extent of initial lung lesion caused by BHT and time interval between BHT administration and beginning of O2 exposure. Potentiation of lung fibrosis was also observed in animals treated with methylcyclopentadienyl manganese tricarbonyl and 70% O2. O2 severely aggravated lung damage caused by bloodborne agents and severity of 2 resulting lesion was determined by many variables.