title: Protective effect of N-acetylcysteine on liver damage during chronic intrauterine hypoxia in fetal guinea pig.
abstract: Chronic exposure to hypoxia during pregnancy generates a stressed intrauterine environment that may lead to fetal organ damage. The objectives of the study are (1) to quantify the effect of chronic hypoxia in the generation of oxidative stress in fetal guinea pig liver and (2) to test the protective effect of antioxidant treatment in hypoxic fetal liver injury. Pregnant guinea pigs were exposed to either normoxia (NMX) or 10.5% O(2) (HPX, 14 days) prior to term (65 days) and orally administered N-acetylcysteine ([NAC] 10 days). Near-term anesthetized fetuses were excised and livers examined by histology and assayed for malondialdehyde (MDA) and DNA fragmentation. Chronic HPX increased erythroid precursors, MDA (NMX vs HPX; 1.26 ± 0.07 vs 1.78 ± 0.07 nmol/mg protein; P < .001, mean ± standard error of the mean [SEM]) and DNA fragmentation levels in fetal livers (0.069 ± 0.01 vs 0.11 ± 0.005 OD/mg protein; P < .01). N-acetylcysteine inhibited erythroid aggregation and reduced (P < .05) both MDA and DNA fragmentation of fetal HPX livers. Thus, chronic intrauterine hypoxia generates cell and nuclear damage in the fetal guinea pig liver. Maternal NAC inhibited the adverse effects of fetal liver damage suggestive of oxidative stress. The suppressive effect of maternal NAC may implicate the protective role of antioxidants in the prevention of liver injury in the hypoxic fetus.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland, Baltimore, MD, USA.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Gerard
authors.initials: G
authors.lastname: Pinkas
authors.forename: LaShauna
authors.initials: L
authors.lastname: Evans
authors.forename: Hongshan
authors.initials: H
authors.lastname: Liu
authors.forename: Yazan
authors.initials: Y
authors.lastname: Al-Hasan
authors.forename: Loren P
authors.initials: LP
authors.lastname: Thompson
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005311:Fetal Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D000111:Acetylcysteine