Effects of ibuprofen (I), a cyclooxygenase inhibitor, and of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, on bleomycin (B) and hyperoxia (H) induced acute lung damage and mortality were studied in hamsters. Hamsters, after receiving bleomycin, 0.25 unit, intratracheally were treated subcutaneously with vehicle (BHV group), ibuprofen, 10 mg/kg, (BHI group) or NDGA 10 mg/kg (BHNDGA group) and then exposed to 70% oxygen (O2) for 72 h. Daily treatment in each case continued for 14 days. The cumulative mortality at 0, 2, 4, 7, and 14 days after O2 exposure was as follows: 0, 5, 13, 26, and 50% in BHV; 0, 10, 21, 33, and 67% in BHI; and 2, 21, 51, 71, and 92% in BHNDGA groups, respectively. The lung hydroxyproline content in pooled control hamsters averaged 721.1 ± 22.3(SE)mg/lung. The lung hydroxyproline content in animals in BHV, BHI, and BHNDGA groups was significantly increased at 4, 7, and 14 days after exposure when compared to controls. There were, however, no significant differences in the hydroxyproline content of the lungs among animals in BHV, BHI, and BHNDGA groups at any post-exposure time. Morphology of lungs of the BHV group showed an infiltrate of monocytes, lymphocytes, and some neutrophils (PMN) at 2 days but was composed primarily of monocytes and macrophages at 4, 7, and 14 days post-exposure. Multifocal fibrosis was observed at 7 days and was more diffuse by 14 days. Multifocal fibrosis in lungs from the BHI group was seen at 4 days with foci being larger at 7 and 14 days. Multifocal epithelial necrosis was observed at 14 days. Lungs from hamsters in the BHNDGA group showed mild airspace dilatation and septa loss at 2 and 4 days that was more severe at 7 days. PMN comprised most of the infiltrate at 0, 2, and 4 days. Diffuse lung fibrosis was only observed in hamsters surviving to 14 days post-exposure. However, multifocal epithelial necrosis was observed at 4 days which became more severe at 14 days. It was concluded that the use of cyclooxygenase or lipoxygenase inhibitors increases acute lung damage and mortality of the bleomycin and hyperoxia model of lung fibrosis.
- Acute lung damage
- Nordihydroguaiaretic acid
ASJC Scopus subject areas
- Pathology and Forensic Medicine