Magnesium sulphate can alleviate oxidative stress and reduce inflammatory cytokines in rat placenta of intrahepatic cholestasis of pregnancy model

Arch Gynecol Obstet. 2018 Sep;298(3):631-638. doi: 10.1007/s00404-018-4850-1. Epub 2018 Jul 23.

Abstract

Purpose: In our study, we try to investigate whether magnesium sulphate (MgSO4) could provide protection against oxidative damage and inflammatory response in rat placenta of intrahepatic cholestasis of pregnancy (ICP) model.

Methods: The rat model of ICP was established by injecting s.c. 17α-ethinyl estradiol (EE) daily for 5 days. MgSO4, as an therapeutic drug for ICP, was injected i.p. daily for 3 days. Age-matched pregnant rats served as controls. The level of serum total bile acid (TBA) was measured. The data including the number and weight of offsprings on day 20 of pregnancy were collected. We observed ultrastructural changes of mitochondria and endoplasmic reticulum (ER) in placenta by transmission electron microscope. The antioxidant proteins peroxiredoxin-6 (Prdx6) and nuclear factor erythroid 2-related factor-2 (Nrf2) were analyzed by Western Blot. The inflammatory cytokines including IL-1β, TNF-α and IFN-γ were investigated by real-time PCR (RT-PCR) and enzyme-linked immune-sorbent assay (ELISA).

Results: The weight of offsprings on day 20 of pregnancy increased in ICP rats treated with MgSO4 (ICP + MG group) compared with that in ICP rats (ICP group). However, the level of TBA was not reduced. The damage of mitochondria and ER was observed in placenta, which was much more slighter in ICP + MgSO4 group as compared with that in ICP group. Prdx6 and Nrf2 were increased, while the inflammatory cytokines including IL-1β, TNF-α and IFN-γ were decreased in ICP + MgSO4 group compared with that in ICP group.

Conclusions: MgSO4 had beneficial effect on improving growth of offsprings in rat model of ICP. The protective effect of MgSO4 on alleviating oxidative damage and inflammatory response in placenta may play an important role in the process. MgSO4 may improve the function of placenta.

Keywords: Inflammatory cytokines; Intrahepatic cholestasis of pregnancy; Magnesium sulphate; Oxidative stress; Placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Cholestasis, Intrahepatic / drug therapy*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Ethinyl Estradiol / pharmacology
  • Female
  • Magnesium Sulfate / pharmacology*
  • Mitochondria / pathology
  • Oxidative Stress / drug effects*
  • Placenta / metabolism
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Bile Acids and Salts
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Ethinyl Estradiol
  • Magnesium Sulfate

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy