Abstract
Objective: To determine if a new class of agents, the 21-aminosteroids, which are reportedly potent inhibitors of iron-dependent lipid peroxidation, could protect rats from bleomycin-induced pulmonary fibrosis. Subjects: Fifty-five adult male Sprague-Dawley rats. Design: Prospective, randomized, blinded, controlled trial. Interventions: The rats were subjected to intratracheal bleomycin (or saline vehicle), and were then treated with the 21-aminosteroid, U74389F (20 mg/kg/day), or vehicle, for the next 7 days. Measurements and Main Results: At 21 days after bleomycin administration, pulmonary fibrosis was assessed histologically as percent of lung fields with evidence of fibrosis. Pulmonary fibrosis was assessed biochemically by measuring pulmonary elastin and hydroxyproline content. To determine if a protective effect of U74389F was linked to the 21-aminosteroid's ability to suppress lipid peroxidation, two products of lipid peroxidation were assayed in the lungs at 7 and 14 days after bleomycin exposure. By histologic assessment, the 21-aminosteroid-treated, bleomycin-exposed animals were found to have significantly decreased the extent of pulmonary fibrosis when compared with the bleomycin control group (mean 48.6 ± 20.0 [SD] % [n = 9] vs. 68.4 ± 19.6% [n = 11]; p < .05). In addition, lung elastin was decreased by ~75% (p < .05) and hydroxyproline was decreased by ~50% (NS) in the 21- aminosteroid-treated group when compared with the bleomycin control group. At 7 and 14 days after bleomycin exposure, all bleomycin-exposed animals had evidence of increased lipid peroxidation (conjugated dienes and thiobarbituric acid-reactive substances), but the 21-aminosteroid-treated, bleomycin-exposed animals had significantly decreased evidence of lipid peroxidation when compared with bleomycin controls. Conclusions: The 21- aminosteroid can substantially protect animals from bleomycin-induced pulmonary fibrosis and may prove useful in other lung diseases where iron- dependent, free-radical reactions and/or lipid peroxidation are presumed mechanisms of toxicity.
| Original language | English |
|---|---|
| Pages (from-to) | 313-319 |
| Number of pages | 7 |
| Journal | Critical Care Medicine |
| Volume | 22 |
| Issue number | 2 |
| State | Published - Jan 1 1994 |
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Keywords
- bleomycin
- cardiopulmonary emergencies
- critical illness
- iron chelation
- lipid peroxidation
- lung injury
- lungs
- malondialdehyde
- oxygen radicals
- pulmonary fibrosis
- respiratory failure
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
Cite this
Effects of the 21-aminosteroid, U74389F, on bleomycin-induced pulmonary fibrosis in rats. / McLaughlin, Gwenn E; Frank, L.
In: Critical Care Medicine, Vol. 22, No. 2, 01.01.1994, p. 313-319.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of the 21-aminosteroid, U74389F, on bleomycin-induced pulmonary fibrosis in rats
AU - McLaughlin, Gwenn E
AU - Frank, L.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Objective: To determine if a new class of agents, the 21-aminosteroids, which are reportedly potent inhibitors of iron-dependent lipid peroxidation, could protect rats from bleomycin-induced pulmonary fibrosis. Subjects: Fifty-five adult male Sprague-Dawley rats. Design: Prospective, randomized, blinded, controlled trial. Interventions: The rats were subjected to intratracheal bleomycin (or saline vehicle), and were then treated with the 21-aminosteroid, U74389F (20 mg/kg/day), or vehicle, for the next 7 days. Measurements and Main Results: At 21 days after bleomycin administration, pulmonary fibrosis was assessed histologically as percent of lung fields with evidence of fibrosis. Pulmonary fibrosis was assessed biochemically by measuring pulmonary elastin and hydroxyproline content. To determine if a protective effect of U74389F was linked to the 21-aminosteroid's ability to suppress lipid peroxidation, two products of lipid peroxidation were assayed in the lungs at 7 and 14 days after bleomycin exposure. By histologic assessment, the 21-aminosteroid-treated, bleomycin-exposed animals were found to have significantly decreased the extent of pulmonary fibrosis when compared with the bleomycin control group (mean 48.6 ± 20.0 [SD] % [n = 9] vs. 68.4 ± 19.6% [n = 11]; p < .05). In addition, lung elastin was decreased by ~75% (p < .05) and hydroxyproline was decreased by ~50% (NS) in the 21- aminosteroid-treated group when compared with the bleomycin control group. At 7 and 14 days after bleomycin exposure, all bleomycin-exposed animals had evidence of increased lipid peroxidation (conjugated dienes and thiobarbituric acid-reactive substances), but the 21-aminosteroid-treated, bleomycin-exposed animals had significantly decreased evidence of lipid peroxidation when compared with bleomycin controls. Conclusions: The 21- aminosteroid can substantially protect animals from bleomycin-induced pulmonary fibrosis and may prove useful in other lung diseases where iron- dependent, free-radical reactions and/or lipid peroxidation are presumed mechanisms of toxicity.
AB - Objective: To determine if a new class of agents, the 21-aminosteroids, which are reportedly potent inhibitors of iron-dependent lipid peroxidation, could protect rats from bleomycin-induced pulmonary fibrosis. Subjects: Fifty-five adult male Sprague-Dawley rats. Design: Prospective, randomized, blinded, controlled trial. Interventions: The rats were subjected to intratracheal bleomycin (or saline vehicle), and were then treated with the 21-aminosteroid, U74389F (20 mg/kg/day), or vehicle, for the next 7 days. Measurements and Main Results: At 21 days after bleomycin administration, pulmonary fibrosis was assessed histologically as percent of lung fields with evidence of fibrosis. Pulmonary fibrosis was assessed biochemically by measuring pulmonary elastin and hydroxyproline content. To determine if a protective effect of U74389F was linked to the 21-aminosteroid's ability to suppress lipid peroxidation, two products of lipid peroxidation were assayed in the lungs at 7 and 14 days after bleomycin exposure. By histologic assessment, the 21-aminosteroid-treated, bleomycin-exposed animals were found to have significantly decreased the extent of pulmonary fibrosis when compared with the bleomycin control group (mean 48.6 ± 20.0 [SD] % [n = 9] vs. 68.4 ± 19.6% [n = 11]; p < .05). In addition, lung elastin was decreased by ~75% (p < .05) and hydroxyproline was decreased by ~50% (NS) in the 21- aminosteroid-treated group when compared with the bleomycin control group. At 7 and 14 days after bleomycin exposure, all bleomycin-exposed animals had evidence of increased lipid peroxidation (conjugated dienes and thiobarbituric acid-reactive substances), but the 21-aminosteroid-treated, bleomycin-exposed animals had significantly decreased evidence of lipid peroxidation when compared with bleomycin controls. Conclusions: The 21- aminosteroid can substantially protect animals from bleomycin-induced pulmonary fibrosis and may prove useful in other lung diseases where iron- dependent, free-radical reactions and/or lipid peroxidation are presumed mechanisms of toxicity.
KW - bleomycin
KW - cardiopulmonary emergencies
KW - critical illness
KW - iron chelation
KW - lipid peroxidation
KW - lung injury
KW - lungs
KW - malondialdehyde
KW - oxygen radicals
KW - pulmonary fibrosis
KW - respiratory failure
UR - http://www.scopus.com/inward/record.url?scp=0028107170&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028107170&partnerID=8YFLogxK
M3 - Article
C2 - 7508358
AN - SCOPUS:0028107170
VL - 22
SP - 313
EP - 319
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 2
ER -