Non-lethal hyperoxic potentiation of lung disease in the rat following subcutaneous administration of bleomycin.
Rats were treated with subcutaneous injections of either saline or 1, 3, or 5 units of bleomycin (BLM) each day for 5 days (5, 15, or 25 units total dose). One half of each group of animals was exposed to 80% oxygen for 4 days during BLM dosings. Rats treated with both 25 units BLM and hyperoxia died after being returned to room air. All remaining rats were sacrificed 6 weeks following the end of treatment. Of the BLM rats in room air, only the lungs of the 15-unit group exhibited histological change, a mild diffuse interstitial disease. Both lower dose groups demonstrated slight increases in hydroxy-proline (OHP) content, a marker of collagen deposition or lung injury. The lungs of BLM rats exposed to hyperoxia demonstrated greater increases in total lung OHP levels. The lungs of the 15-unit group demonstrated lesions consistent with diffuse interstitial pulmonary fibrosis. Short-term, sublethal hyperoxia clearly potentiated injury in the rat following subcutaneous BLM treatment as assessed by either lethality or markers of pulmonary pathology.
Coursin
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Department of Anesthesiology, University of Wisconsin Clinical Science Center, Madison 53792.
Cihla
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D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D004357:Drug Synergism; D006909:Hydroxyproline / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D001761:Bleomycin; D006909:Hydroxyproline; D010100:Oxygen