Related Experiment Videos
Intraamniotic endotoxin increases lung antioxidant enzyme activity in preterm lambs
Ilene R S Sosenko1, Alan H Jobe
1Division of Neonatology, Department of Pediatrics, University of Miami School of Medicine, Florida 33101, USA. isosenko@miami.edu
Pediatric Research
|March 4, 2003
Summary
Intraamniotic endotoxin accelerates fetal lung antioxidant enzyme activity, similar to its effects on lung function and surfactant maturation. This maturation process is driven by inflammation, not fetal cortisol.
Area of Science:
- Fetal Physiology
- Pulmonary Medicine
- Biochemistry
Background:
- Intraamniotic endotoxin administration is known to enhance fetal lung maturation, improving lung function and surfactant production in sheep.
- The precise mechanisms, particularly concerning the antioxidant enzyme (AOE) system, remain largely unexplored.
- This study investigates the impact of endotoxin on the development of fetal lung AOE activity.
Purpose of the Study:
- To determine if intraamniotic endotoxin administration accelerates the maturation of the antioxidant enzyme system in fetal sheep lungs.
- To compare the effective doses and timing of endotoxin administration for AOE system maturation with those for lung function and surfactant maturation.
- To elucidate the role of proinflammatory stimulation versus glucocorticoid hormones in fetal lung AOE system development.
Main Methods:
- Dose-response study: Fetal sheep at 125 days gestation received intraamniotic injections of Escherichia coli endotoxin (1, 4, 20, or 100 mg) 7 days before preterm delivery.
- Time-interval study: A fixed dose of 20 mg endotoxin was administered at varying intervals (1, 2, 4, 7, or 15 days) before preterm delivery.
- Measurement of key antioxidant enzymes: Glutathione peroxidase, catalase, and superoxide dismutase activities were quantified in lung tissue.
Main Results:
- Significant increases in glutathione peroxidase, catalase, and superoxide dismutase activities were observed in response to specific endotoxin doses.
- Elevated enzyme activities were detected within 2-7 days post-administration, with no sustained increases at 15 days.
- The effective doses and administration intervals for AOE maturation mirrored those previously reported for lung function and surfactant maturation.
Conclusions:
- Intraamniotic endotoxin administration effectively accelerates the maturation of the fetal sheep lung's antioxidant enzyme system.
- Proinflammatory pathways, independent of fetal cortisol, are implicated in the maturation of the lung's antioxidant defense mechanisms.
- These findings suggest a common inflammatory mechanism underlies both functional and antioxidant maturation of the fetal lung.