Abstract
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 bleomycin exposure, the 21-aminosteroid-treated animals had decreased evidence of DNA injury, expressed as percentage of DNA fragmentation normalized to the control group (113.5 ± 6 [SEM] vs. 132 ± 3.9%, p ≤ .05), and activity of the DNA repair enzyme poly ADP-ribose synthetase (3.4 ± 0.2 vs. 5.0 ± 0.9 pmol nicotinamide adenine dinucleotide/min/mg protein, p ≤ .05). Only bleomycin- exposed (+ vehicle) animals demonstrated significant evidence of increased DNA injury vs. the intratracheal saline-exposed control groups. Conclusions: The 21-aminosteroid pretreatment decreases subsequent pulmonary DNA injury induced by bleomycin exposure. This finding is likely due to the 21- aminosteroid's iron-chelating and cell-permeating abilities, and suggests that these agents may be effective in other diseases where iron-dependent free radical reactions occur.
| Original language | English |
|---|---|
| Pages (from-to) | 652-656 |
| Number of pages | 5 |
| Journal | Critical Care Medicine |
| Volume | 25 |
| Issue number | 4 |
| State | Published - Apr 1 1997 |
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Keywords
- bleomycin
- DNA fragmentation
- iron chelation
- lipid peroxidation
- lung injury
- oxygen free radicals
- poly(ADP-ribose) synthetase
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
Cite this
Reduction of bleomycin-induced acute DNA injury in the rat lung by the 21-aminosteroid, U-74389G. / Dallessio, Joseph J.; McLaughlin, Gwenn E; Frank, Lee.
In: Critical Care Medicine, Vol. 25, No. 4, 01.04.1997, p. 652-656.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduction of bleomycin-induced acute DNA injury in the rat lung by the 21-aminosteroid, U-74389G
AU - Dallessio, Joseph J.
AU - McLaughlin, Gwenn E
AU - Frank, Lee
PY - 1997/4/1
Y1 - 1997/4/1
N2 - 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 bleomycin exposure, the 21-aminosteroid-treated animals had decreased evidence of DNA injury, expressed as percentage of DNA fragmentation normalized to the control group (113.5 ± 6 [SEM] vs. 132 ± 3.9%, p ≤ .05), and activity of the DNA repair enzyme poly ADP-ribose synthetase (3.4 ± 0.2 vs. 5.0 ± 0.9 pmol nicotinamide adenine dinucleotide/min/mg protein, p ≤ .05). Only bleomycin- exposed (+ vehicle) animals demonstrated significant evidence of increased DNA injury vs. the intratracheal saline-exposed control groups. Conclusions: The 21-aminosteroid pretreatment decreases subsequent pulmonary DNA injury induced by bleomycin exposure. This finding is likely due to the 21- aminosteroid's iron-chelating and cell-permeating abilities, and suggests that these agents may be effective in other diseases where iron-dependent free radical reactions occur.
AB - 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 bleomycin exposure, the 21-aminosteroid-treated animals had decreased evidence of DNA injury, expressed as percentage of DNA fragmentation normalized to the control group (113.5 ± 6 [SEM] vs. 132 ± 3.9%, p ≤ .05), and activity of the DNA repair enzyme poly ADP-ribose synthetase (3.4 ± 0.2 vs. 5.0 ± 0.9 pmol nicotinamide adenine dinucleotide/min/mg protein, p ≤ .05). Only bleomycin- exposed (+ vehicle) animals demonstrated significant evidence of increased DNA injury vs. the intratracheal saline-exposed control groups. Conclusions: The 21-aminosteroid pretreatment decreases subsequent pulmonary DNA injury induced by bleomycin exposure. This finding is likely due to the 21- aminosteroid's iron-chelating and cell-permeating abilities, and suggests that these agents may be effective in other diseases where iron-dependent free radical reactions occur.
KW - bleomycin
KW - DNA fragmentation
KW - iron chelation
KW - lipid peroxidation
KW - lung injury
KW - oxygen free radicals
KW - poly(ADP-ribose) synthetase
UR - http://www.scopus.com/inward/record.url?scp=0030971425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030971425&partnerID=8YFLogxK
M3 - Article
C2 - 9142031
AN - SCOPUS:0030971425
VL - 25
SP - 652
EP - 656
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 4
ER -