Antenatal cocaine exposure produces accelerated surfactant maturation without stimulation of antioxidant enzyme development in the late gestation rat.
Antenatal cocaine administration is associated with increases in catecholamines and glucocorticoids and results in fetal hypoxemia, with the speculated potential for increased free radical formation in the fetus. Because of this, we hypothesized that antenatal cocaine exposure would produce not only accelerated pulmonary surfactant maturation, but also stimulation of antioxidant enzyme (AOE) system maturation and the ability to mount a protective AOE response to hyperoxia as well. Seventy-two, 48, and 24 h before delivery at either 20, 21, or 22 d of gestation, pregnant rats received twice daily s.c. injections of cocaine hydrochloride (40 mg/kg) or saline. Off-spring demonstrated growth retardation with significant reduction in body weight at all 3 gestational d studied that persisted to the 5th postnatal d. Serum corticosterone and total catecholamines were elevated from 50 to 200% in cocaine-exposed adult rats and pups. Advanced surfactant development in cocaine-exposed fetal offspring was apparent at d 21 of gestation, with significant increases in lung disaturated phosphatidylcholine content in cocaine (3.94 +/- 0.67 mg/g lung) versus control (3.25 +/- 0.64) offspring (p < 0.01). No increases in AOE maturation were found in cocaine-exposed fetuses at all 3 gestational d studied, whereas a significant decrease was demonstrated in glutathione peroxidase activity at d 20 and 22 of gestation in cocaine-exposed fetuses. In addition, cocaine newborns manifested a protective AOE response to hyperoxia of a magnitude similar to that of control newborns.(ABSTRACT TRUNCATED AT 250 WORDS)
Sosenko
I R
IR
Department of Pediatrics, University of Miami School of Medicine, Florida 33101.
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D003042:Cocaine / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005325:Fetal Organ Maturity / Q000187:drug effects; D005333:Fetus / Q000187:drug effects*; D005865:Gestational Age; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002395:Catecholamines; D011663:Pulmonary Surfactants; D003042:Cocaine; D003345:Corticosterone