Female Wistar rats (n = 11) received bleomycin 10 mg kg-1 i.p. three times weekly for 6 weeks. Four weeks later part of the group (n = 7) were exposed to 50% oxygen in air for 4 h; the others served as unexposed controls. A further control group (n = 5) received physiological saline i.p. and was not exposed to oxygen. One week after the hyperoxia treatment all animals were sacrificed and the lungs prepared for histological and biochemical determinations. Although the average body weight of the bleomycin-treated rats decreased significantly compared with the saline-treated controls, no significant alterations in lung histology were found in regard to the occurrence of oedema, fibrosis, and type II pneumocytes. Intra-alveolar macrophages were significantly increased. Subsequent hyperoxia did not lead to a more pronounced effect, except for macrophage accumulation. The activities of superoxide dismutase and glutathione peroxidase were not changed either after administration of bleomycin alone or after combination with hyperoxia. It is concluded that bleomycin i.p. in doses comparable to those encountered clinically, administered alone or combined with hyperoxia, does not result in pulmonary damage in female Wistar rats.
Bleomycin 0.4, 0.6, 1.0 or 3.5 mg/kg body weight was administered via the trachea in rats. After various time intervals some of the animals were exposed to 50% oxygen for either 4 or 24 h. The rats were then sacrificed at different times. Control rats remained untreated or received physiological saline. Lung histology was studied by light microscopy. In a number of rats the lung content of hydroxyproline was determined. Mild reactions, namely increases in pneumocytes type II and macrophages, oedema and prefibrotic alterations were observed after the instillation of bleomycin. The reactions were comparable to those observed after additional hyperoxia alone. Lung hydroxyproline concentration was not increased after bleomycin plus oxygen as compared with bleomycin alone. We conclude that no added toxicity is caused by 50% oxygen supplied for 4 or 24 h subsequent to doses of bleomycin that lead to mild pulmonary abnormalities in the absence of hyperoxia.
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