Amifostine modulation of bleomycin-induced lung injury in rodents

Bleomycin is an effective anticancer agent whose treatment is limited by severe and potentially fatal pulmonary toxicity. This toxicity, characterized by alveolar inflammation and proliferative fibrosis, is mediated by active oxygen species and may result in disruption of the balance between type 2 pneumocyte apoptosis and fibroblast proliferation. The chemoprotectant activity of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) is attributed, in part, to the scavenging of active oxygen species. Therefore, it was of interest to study the effects of amifostine on ameliorating the pulmonary toxicities associated with bleomycin in animals. Studies in hamsters and mice demonstrate that pretreatment with amifostine reduces the pulmonary toxicity induced by bleomycin administration. The results of these preclinical studies suggest that amifostine may be clinically beneficial in reducing the severe pulmonary toxicity associated with bleomycin.