Exacerbation of bleomycin-induced lung injury in mice by amifostine.
Bleomycin (BLM) induces lung injury and fibrosis in the murine lung and enhances tumor necrosis factor (TNF)-alpha and collagen mRNA expression in the murine lung. Amifostine is a cytoprotective agent that protects normal tissues from the cytotoxic effects of chemo- and radiation therapy. We investigated the effect of amifostine in BLM-induced lung injury in mice. Mice received intraperitoneal amifostine (200 mg/kg) 30 min before and/or 1, 3, and 7 days after an intratracheal injection of saline or BLM (4 U/kg). The animals were killed 14 days after BLM exposure, and their lungs were studied for TNF-alpha and collagen mRNA expression, hydroxyproline content, and histopathology. Light microscopy demonstrated that amifostine exacerbated the BLM-induced lung injury in mice. Increased TNF-alpha mRNA expression as a result of BLM exposure was not modulated by amifostine treatment. In contrast, amifostine treatment enhanced the BLM-induced expression of alpha(1)(I) procollagen mRNA in the lung. Similarly, mice treated with amifostine before BLM exposure accumulated significantly higher amounts of hydroxyproline (111 +/- 5 microg/lung) than BLM-treated animals (90 +/- 6 microg/lung). These data suggest that amifostine treatment exacerbates BLM-induced lung injury in mice.
Ortiz
L A
LA
Section of Pulmonary Diseases, Critical Care, and Environmental Medicine, New Orleans, Louisiana 70112, USA. lortiz@mailhost.tcs.tulane.edu
Lasky
J A
JA
Safah
H
H
Reyes
M
M
Miller
A
A
Lungarella
G
G
Friedman
M
M
D004999:Amifostine / Q000009:adverse effects*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D003094:Collagen / Q000235:genetics; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011837:Radiation-Protective Agents / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D003094:Collagen; D004999:Amifostine; D006909:Hydroxyproline