Modulation of bleomycin-induced pulmonary toxicity in the hamster by the antioxidant amifostine

✍ Scribed by Linda Nici; Anabela Santos-Moore; Charles Kuhn; Paul Calabresi

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 186 KB
• Volume: 83
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/(sici)1097-0142(19981101)83:9<2008::aid-cncr18>3.0.co;2-m

✦ Synopsis

BACKGROUND.

Bleomycin produces lung fibrosis in a wide variety of species. In humans, it can cause significant morbidity and mortality when used to treat malignancies such as lymphoma and testicular carcinoma. In rodents, it has been extensively used to study key mechanisms of lung injury and repair. Bleomycin pulmonary toxicity is mediated, at least in part, by the generation of active oxygen species. Amifostine, an aminothiol compound, is a cytoprotectant that is used with many antitumor agents and can act as a potent scavenger of free radicals. The authors hypothesized that amifostine could ameliorate bleomycin lung injury.

METHODS.

Hamsters weighing 120 g were given an intraperitoneal (IP) injection of amifostine (200 mg/kg, 1180 mg/m 2 ) or saline with intratracheal (IT) bleomycin (1 unit) or saline, followed by daily IP amifostine or saline for 6 days. Lungs were assessed on Day 2 for acute lung injury, which was determined by wet-to-dry lung weight ratios. On Day 21, histologic assessment of fibrosis and biochemical analysis of lung hydroxyproline content were performed.