Oxidative stress after antenatal betamethasone: acute downregulation of glutathione peroxidase-3

Early Hum Dev. 2009 Dec;85(12):767-71. doi: 10.1016/j.earlhumdev.2009.10.005. Epub 2009 Nov 17.

Abstract

Background: Human and experimental data show that antenatal exposure to glucocorticoids (GC) temporarily reduces fetal well-being and impairs the fetal response to hypoxemia.

Aims: We tested the hypothesis that antenatal betamethasone provokes transient oxidative stress, which may be triggered directly by the GC or indirectly by metabolic signals such as increased glucose and free fatty acid (FFA) concentrations.

Study design: Prospective (single center, 18 months) cohort study in newborns <34 weeks gestational age at birth.

Methods: We studied 105 newborns and measured oxidative damage to lipids [malondialdehyde (MDA)] and proteins (protein carbonyls), as well as glutathione peroxidase-3 (GPx3), an important antioxidant enzyme, in umbilical vein (UV) plasma. In addition, we measured umbilical artery and UV blood gases, and metabolic indices (plasma glucose, FFA and insulin) in UV.

Results: MDA but not protein carbonyl concentrations was inversely related to time elapsed since the first or last betamethasone administration (p=0.006); MDA remained elevated by 69-96% for at least 72 h after the last betamethasone. By contrast, GPx3 concentrations were repressed in newborns who received betamethasone < or =24h before birth. GPx3 and MDA concentrations were correlated (r=-0.38, p<0.001). Labor, GA, sex, size at birth, blood gases or metabolic indices did not explain the effects of betamethasone on MDA and GPx3.

Conclusions: Antenatal GC elicit a rapid suppression of the GPx3 antioxidant defense system which may contribute to a longer-lasting but also transient rise in lipid oxidative damage.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Betamethasone / administration & dosage
  • Betamethasone / adverse effects
  • Betamethasone / pharmacology*
  • Blood Chemical Analysis
  • Down-Regulation / drug effects
  • Female
  • Fetal Blood / chemistry
  • Fetal Blood / drug effects
  • Fetal Blood / metabolism
  • Glutathione Peroxidase / blood*
  • Glutathione Peroxidase / metabolism
  • Humans
  • Infant, Newborn
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Prenatal Exposure Delayed Effects / blood*
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / enzymology
  • Time Factors
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Betamethasone
  • GPX3 protein, human
  • Glutathione Peroxidase