Evaluation of oxidative stress in placenta of fetal cardiac dysfunction rat model and antioxidant defenses of maternal vitamin C supplementation with the impacts on P-glycoprotein

J Obstet Gynaecol Res. 2014 Jun;40(6):1632-42. doi: 10.1111/jog.12389.

Abstract

Aim: The oxidative stress of placenta during fetal heart dysfunction (FHD) is lack of evaluation. So, we carried out an experiment to explore whether vitamin C (VitC) can be supplied for placental protection under FHD and its impacts on P-glycoprotein expression.

Methods: Fetal heart dysfunction was induced by two intra-amniotic injections of isoproterenol, then (VitC) was supplied. Hematoxylin-eosin (HE) staining was used to evaluate placental histology, and oxidative stress was measured by total antioxidant capacity, total superoxide dismutase and level of advanced oxidation protein products (AOPP), as well as apoptosis rate. Real-time polymerase chain reaction was adopted to measure the expressions of superoxide dismutase-1 (Sod-1), glutathione peroxidase-1 (Gpx-1) and endothelial nitric oxide synthase (eNOS) in placenta. Finally, western blot was performed to detect P-glycoprotein expression.

Results: All isoproterenol twice-treated fetuses exhibited significant (P < 0.05) contractile dysfunction by fetal echocardiography compared to others. The HE staining showed severe placental hydrops in the FHD group, and that hydrops could be reduced by VitC treatment. Total antioxidant capacity and total Sod-1 decreased in FHD and elevated after VitC supplementation. Also, level of AOPP increased in FHD and dropped after VitC supplementation. Analysis of apoptosis demonstrated that there was a mild increase in apoptosis rate of FHD. Reductions of Sod-1 and eNOS mRNA expression were confirmed in FHD, but these could recovered after VitC supplementation, with the same tendency of the P-glycoprotein.

Conclusion: Severe oxidative injuries were identified in placentas of FHD with P-glycoprotein repression. VitC administration can reduce the oxidative stress and rebuild the protective mechanism of placenta.

Keywords: P-glycoprotein; fetal heart dysfunction; oxidative stress; placenta; vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Disease Models, Animal
  • Echocardiography
  • Female
  • Fetal Diseases / diagnostic imaging
  • Fetal Diseases / metabolism*
  • Heart Failure / diagnostic imaging
  • Heart Failure / metabolism*
  • Oxidative Stress / drug effects*
  • Placenta / drug effects
  • Placenta / metabolism
  • Placenta / pathology
  • Placenta Diseases / metabolism
  • Placenta Diseases / pathology
  • Placenta Diseases / prevention & control*
  • Polymerase Chain Reaction
  • Pregnancy
  • Rats, Sprague-Dawley

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antioxidants
  • Ascorbic Acid