Deferoxamine infusion does not inhibit bleomycin-induced lung damage in the rat.
It has been proposed that the pneumonitis and subsequent lung fibrosis induced by bleomycin occurs when bleomycin is complexed with ferrous iron and oxygen. In order to see whether chelation of free iron reduced tissue damage induced by intratracheal bleomycin, deferoxamine (DFO) was administered by continuous subcutaneous infusion to overcome its rapid renal excretion. Thirty-three rats received DFO and 30 rats received an equivalent volume of saline by 7-day infusion pumps. Three days after commencement of infusion, half of each group received intratracheal bleomycin, the remainder received intratracheal saline. Three weeks after intratracheal injection, the rats were killed and their lungs were removed for histologic and morphometric assessment and collagen estimation. When compared with animals given intratracheal saline, both bleomycin-treated groups had significant evidence of lung toxicity, but DFO was not protective. Similarly, DFO infusion did not reduce the elevation in collagen concentration (bleomycin/saline, 49 +/- 3.6; bleomycin/DFO, 49.8 +/- 4.1; saline/saline, 39.6 +/- 3.9; saline/DFO, 43.4 +/- 3.8 mg.g-1 wet lung weight) or total lung collagen (bleomycin/saline, 29.9 +/- 6.3; bleomycin/DFO, 33.7 +/- 1.8; saline/saline, 15.5 +/- 2.2; saline/DFO, 17.8 +/- 1.9 mg.left lung-1) induced by bleomycin. This lack of effect was not due to iron contamination of the DFO in the pump or to loss of chelation capacity of DFO, at least for as long as 6 days after pump implantation. No DFO was detected in homogenized lung tissue (limits of detection of assay was 8 x 10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Ward
H E
HE
Department of Medicine, University of Sydney, Australia.
Hicks
M
M
Nicholson
A
A
Berend
N
N
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003676:Deferoxamine / Q000032:analysis / Q000494:pharmacology*; D007260:Infusion Pumps; D007501:Iron / Q000032:analysis; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D009994:Osmolar Concentration; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012996:Solutions / Q000032:analysis
D012996:Solutions; D001761:Bleomycin; D007501:Iron; D003676:Deferoxamine