The Effect of Deferoxamine on Bleomycin-induced Lung Fibrosis in the Hamster

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Abstract
Bleomycin is a commonly used antineoplastic compound that produces a dose-and time-dependent pneumonitis and fibrosis in humans. The mechanism of bleomycin-induced fibrosis is not known. However, the production of O2 radicals by way of a ferrous ion-molecular O2 mechanism might be related to the pulmonary fibrosis. Therefore, the possibility that parenterally administered deferoxamine, an Fe chelating compound, could modulate the morphologic and biochemical estimates of bleomycin-induced lung fibrosis was evaluated in hamsters. Deferoxamine pretreatment and daily injection for 21 days after intratracheally administered bleomycin resulted in a 33% reduction in lung collagen accumulation compared with that after bleomycin treatment alone. However, fibrosis was still present in the bleomycin-deferoxamine group; the animals showed a 142 and 150% increase in lung collagen compared with that in saline and deferoxamine-treated control animals, respectively. Morphologic estimates of the severity of fibrosis in the bleomycin-deferoxamine treatment group were reduced when compared with the bleomycin treatment group alone, but was increased compared with saline- and saline-deferoxamine-treated control animals. Deferoxamine treatment reduces the severity of bleomycin-induced pulmonary fibrosis in hamsters. The mechanism might be by the prevention of Fe catalyzed, free-radical formation.

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