Effects of antenatal dexamethasone on antioxidant enzymes and nitric oxide synthase in the rat lung.
We investigated the effects of prenatal dexamethasone (DEX) administration on antioxidant enzymes (AOEs) and nitric oxide synthase (NOS) in fetal and neonatal rat lungs. DEX (1 mg/kg, s.c., for 2 days) or vehicle alone was administered to pregnant rats, and the lungs of fetuses on days 19 and 21 of gestation and of 1- and 3-day-old neonates were examined. We measured protein levels of the AOEs manganese superoxide dismutase and copper-zinc superoxide dismutase (Mn SOD and Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and inducible and endothelial nitric oxide synthase (i-NOS and e-NOS). Mn SOD, GSH-Px, and e-NOS expression gradually increased with increasing gestational and postnatal age in the lungs of the control groups. Cu-Zn SOD, CAT, and i-NOS expression did not change with increasing gestational and postnatal age in the lungs of the control groups. DEX administration had significant effects on i-NOS and e-NOS protein and mRNA expression. The increased Mn SOD, GSH-Px, and e-NOS expressions during the perinatal period suggests that antenatal developmental changes in AOEs in the lungs of premature fetuses could be reduced by reactive oxygen species-mediated injury at birth. Furthermore, antenatal glucocorticoid treatment may accelerate the development of lungs via the two types of NOS.
Arima
Masaki
M
Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. arima3@marianna-u.ac.jp
Kumai
Toshio
T
Asoh
Kentaro
K
Takeba
Yuko
Y
Murano
Koutaro
K
Goto
Kenjiro
K
Tsuzuki
Yoshimitsu
Y
Mizuno
Masanori
M
Kojima
Takahiro
T
Kobayashi
Shinichi
S
Koitabashi
Yasushi
Y
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase