Reduction of bleomycin-induced acute DNA injury in the rat lung by the 21-aminosteroid, U-74389G.

  title={Reduction of bleomycin-induced acute DNA injury in the rat lung by the 21-aminosteroid, U-74389G.},
  author={Joseph J. Dallessio and Gwenn E Mclaughlin and Lee Frank},
  journal={Critical care medicine},
  volume={25 4},
OBJECTIVE To determine whether pretreatment with a 21-aminosteroid, U-74389G, can prevent subsequent DNA injury in bleomycin-exposed lungs. SUBJECTS Thirty-six adult male Sprague-Dawley rats. DESIGN Controlled animal laboratory investigation of DNA injury in vivo. INTERVENTIONS Animals were treated with 21-aminosteroid (10 mg/kg) or vehicle and subsequently received intratracheal instillation of bleomycin (1.75 U) or normal saline. MEASUREMENTS AND MAIN RESULTS Twenty-four hours after… 
Antioxidants as potential therapeutics for lung fibrosis.
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  • Biology
    Antioxidants & redox signaling
  • 2008
Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis


Effects of the 21‐aminosteroid, U74389F, on bleomycin‐induced pulmonary fibrosis in rats
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.
Acute pulmonary toxicity of bleomycin: DNA scission and matrix protein mRNA levels in bleomycin-sensitive and -resistant strains of mice.
The data demonstrate that BLM treatment rapidly produces extensive pulmonary DNA damage in vivo, that persistence of DNA damage rather than the initial level of strand scission is associated with sensitivity to BLM lung disease in these mice, and that changes in the levels of mRNA encoding pulmonary matrix proteins occur in vivo within 1 to 3 days after intravenous BLM treatment.
Protection against Acute and Chronic Hyperoxic Inhibition of Neonatal Rat Lung Development with the 21-Aminosteroid Drug U74389F
21-AS treatment had a substantial protective effect against both the acute and chronic lung as well as cardiac morphologic changes that early life exposure to hyperoxia can produce.
Effects of the 21-aminosteroid U74006F on experimental head injury in mice.
It is demonstrated that early treatment after severe concussive head injury with a potent inhibitor of iron-dependent lipid peroxidation can significantly benefit the injured brain in mice and promote both early neurological recovery and long-term survival.
Effects of treatment with the 21-aminosteroid, U7438F, on pulmonary cytokine expression following hemorrhage and resuscitation.
Treatment with U74389F, a 21-aminosteroid whose major activity is inhibition of lipid peroxidation due to the generation of reactive oxygen intermediates, significantly decreases hemorrhage-induced activation of proinflammatory cytokine expression among pulmonary cell populations.
Evaluation of antifibrotic drugs in bleomycin-induced pulmonary fibrosis in hamsters.
In the present study, beta-aminopropionitrile, D-penicillamine, and p-aminobenzoic acid were found to reduce significantly the accumulation of neutral salt insoluble collagen in bleomycin-treated animals.
Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis
Results indicate that in response to bleomycin, the T lymphocytes induce an increase of the pulmonary TNF production, which leads to alveolar damage, growth of fibroblast, and collagen deposition, which is almost completely prevented by anti-TNF antibody.
N-acetylcysteine in experimental and clinical acute lung injury.
  • G. Bernard
  • Medicine, Biology
    The American journal of medicine
  • 1991
The Lazaroid U74006F, a 21‐Aminosteroid Inhibitor of Lipid Peroxidation, Attenuates Myocardial Injury from Ischemia and Reperfusion
Pretreatment with U74006F diminished myocardial injury and enhanced systolic and diastolic functional recovery, probably by protecting the lipid component of cell membranes from peroxidation by reactive oxygen metabolites.