title: The effect of indomethacin, prednisolone and cis-4-hydroxyproline on pulmonary fibrosis produced by butylated hydroxytoluene and oxygen.
abstract: The purpose of this study was to examine whether development of pulmonary fibrosis in mice could be influenced by indomethacin, prednisolone or a proline analog. Pulmonary fibrosis was produced in mice treated with butylated hydroxytoluene (BHT) 400 mg/kg and immediately exposed to 80% oxygen for 3 days. This treatment regimen resulted in 47% mortality. Surviving mice exhibited significant accumulations of pulmonary collagen as evidenced by increases in total lung hydroxyproline levels. The administration of indomethacin (4 mg/kg/day) on days 1-6 after BHT decreased mortality to 14% and diminished the accumulation of collagen in lung tissue. Indomethacin also enhanced survival when administered on days 1-3 after BHT/O2 but had no effect on lung collagen levels. Treatment with indomethacin on days 4-6 after BHT had no beneficial effect. The administration of prednisolone (60 mg/kg/day) on days 1-3, 1-6, or 4-6 after BHT decreased mortality but had no effect on accumulation of lung collagen. Cis-4-hydroxyproline (400 mg/kg/day) also had no effect on pulmonary fibrosis but did enhance survival when given on days 1-3 after BHT. Administering prednisolone (60 mg/kg/day) on days 1-6 after BHT to mice left in room air produced significantly more pulmonary fibrosis than in BHT-treated mice given saline. These data support the use of the BHT/O2 model of pulmonary fibrosis for screening potential antifibrotic agents. The possibility that corticosteroid treatment may enhance pulmonary fibrosis in a damaged lung is also demonstrated.
mesh_terms: D000818:Animals; D002084:Butylated Hydroxytoluene / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism; D006909:Hydroxyproline / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000009:adverse effects; D011239:Prednisolone / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D002084:Butylated Hydroxytoluene; D003094:Collagen; D011239:Prednisolone; D006909:Hydroxyproline; D010100:Oxygen; D007213:Indomethacin