The effect of alpha-difluoromethylornithine on the development of bleomycin-induced pulmonary fibrosis in hamsters

The development of bleomycin-induced lung fibrosis was studied in hamsters drinking tap water or 2% alpha-difluoromethylornithine (DFMO) dissolved in tap water for 14 days. The fibrotic lesions in the lung were evaluated by biochemical measurements of total neutral salt soluble (NSS) and insoluble (NSI) collagens and by morphometric histopathologic techniques. Daily ingestion of DFMO failed to offer any protection against bleomycin-induced lung fibrosis; instead, it increased the deposition of total lung NSI collagen to 396% of control, as compared with 145% of control caused by bleomycin treatment alone. Daily intake of DFMO by itself increased the accumulation of total lung NSI collagen to 250% of control, as opposed to a 145% increase caused by bleomycin treatment alone. Histopathologically, the lung lesions in hamsters treated with bleomycin and DFMO were qualitatively similar to those of hamsters treated with bleomycin alone. However, morphometric estimates revealed that of lung lesions were more diffuse and severe in the former than in the latter group.