Prenatal Nicotine Exposure Augments Renal Oxidative Stress in Embryos of Pregnant Rats with Reduced Uterine Perfusion Pressure.
OBJECTIVE
Both maternal nicotine (NIC) exposure and placental insufficiency increase oxidative stress in the fetal kidney ensuing fetal programming of renal diseases in adult life. Their combined effects, however, are unknown. We tested the hypothesis that maternal NIC exposure exacerbates renal oxidative stress and injury in fetuses of pregnant rats with placental insufficiency.


METHODS
Fourteen-day-pregnant rats were subjected to sham operation or reduced uterine perfusion pressure (RUPP) that received either nicotine (20 μg/ml in 1% saccharine) or vehicle (1% saccharine) in their drinking water. At gestational age of 21 days, male fetuses were collected by C-section and sacrificed: plasma and renal cotinine content, extent of renal oxidative stress (4-hydroxynonenal [HNE] and HO-1) and injury (KIM-1) were determined together with the weight of the fetal kidney and fetus.


RESULTS
Prenatal NIC exposure resulted in cotinine accumulation in the plasma and kidney of the fetuses, augmented RUPP-associated increase in renal HNE content and HO-1 expression as well as KIM-1 expression. NIC also enhanced RUPP-induced reduction in fetal and fetal kidney weight.


CONCLUSIONS
Prenatal NIC exposure augments the existing renal risk in the growth-restricted fetus, which may contribute to worsening in fetal programming of renal disease.
Division of Pediatric Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Norma
N
Ojeda
Division of Pediatric Nephrology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Samuel
S
Hall
Division of Pediatric Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Cara J
CJ
Lasley
Division of Pediatric Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Benjamin
B
Rudsenske
Division of Pediatric Nephrology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Mehul
M
Dixit
Division of Pediatric Nephrology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A. iarany@umc.edu.
Istvan
I
Arany
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003367:Cotinine / Q000032:analysis / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010477:Perfusion; D010927:Placental Insufficiency / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology
D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine
Nicotine; fetal; renal oxidative stress