Magnesium sulphate can alleviate oxidative stress and reduce inflammatory cytokines in rat placenta of intrahepatic cholestasis of pregnancy model
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.
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).
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.
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.
KeywordsIntrahepatic cholestasis of pregnancy Magnesium sulphate Placenta Oxidative stress Inflammatory cytokines
We thanked Zhejiang Provincial People’s Hospital and Zhejiang Chinese Medical University for providing assists for our research. We thanked the Department of Health of Zhejiang Province for providing fund for our research.
FH: data collection and analysis, manuscript writing. LHX: data analysis, manuscript revision. YQH: data collection and analysis. TQC: literature collection, data collection. TCZ: data collection. LWY: protocol development, manuscript revision.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest with the contents of this article
This study protocol was approved by the Animal Care Committee of Zhejiang Chinese Medical University. All the experiments were performed according to the approved National Institutional Guidelines for the Care and Use of Laboratory Animals.
- 4.Wu WB, Xu YY, Cheng WW, Wang YX, Liu Y, Huang D, Zhang HJ (2015) Agonist of farnesoid X receptor protects against bile acid induced damage and oxidative stress in mouse placenta—a study on maternal cholestasis model. Placenta 36(5):545–551. https://doi.org/10.1016/j.placenta.2015.02.005 CrossRefPubMedGoogle Scholar
- 5.Ignacio Barrasa J, Olmo N, Perez-Ramos P, Santiago-Gomez A, Lecona E, Turnay J, Antonia Lizarbe M (2011) Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells. Apoptosis 16(10):1054–1067. https://doi.org/10.1007/s10495-011-0633-x CrossRefPubMedGoogle Scholar
- 8.Qu K, Shen NY, Xu XS, Su HB, Wei JC, Tai MH, Meng FD, Zhou L, Zhang YL, Liu C (2013) Emodin induces human T cell apoptosis in vitro by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction. Acta Pharmacol Sin 34(9):1217–1228. https://doi.org/10.1038/aps.2013.58 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Singh SP, Chhunchha B, Fatma N, Kubo E, Singh SP, Singh DP (2016) Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells. Am J Physiol Cell Physiol 310(1):C1–16. https://doi.org/10.1152/ajpcell.00229.2015 CrossRefPubMedGoogle Scholar
- 15.Lee PY, Yang CH, Kao MC, Su NY, Tsai PS, Huang CJ (2015) Phosphoinositide 3-kinase beta, phosphoinositide 3-kinase delta, and phosphoinositide 3-kinase gamma mediate the anti-inflammatory effects of magnesium sulfate. J Surg Res 197(2):390–397. https://doi.org/10.1016/j.jss.2015.04.051 CrossRefPubMedGoogle Scholar
- 19.Zhang Y, Pan Y, Lin C, Zheng Y, Sun H, Zhang H, Wang J, Yuan M, Duan T, Du Q, Chen J (2016) Bile acids evoke placental inflammation by activating Gpbar1/NF-kappaB pathway in intrahepatic cholestasis of pregnancy. J Mol Cell Biol 8(6):530–541. https://doi.org/10.1093/jmcb/mjw025 CrossRefPubMedGoogle Scholar
- 20.Shi Q, Wang J, Yan S, Zhao J, Li H (2014) Expression of neuropeptide Y and pro-opiomelanocortin in hypothalamic arcuate nucleus in 17alpha-ethinyl estradiol-induced intrahepatic cholestasis pregnant rat offspring. J Obstet Gynaecol Res 40(2):445–452. https://doi.org/10.1111/jog.12206 CrossRefPubMedGoogle Scholar
- 26.Acar N, Soylu H, Edizer I, Ozbey O, Er H, Akkoyunlu G, Gemici B, Ustunel I (2014) Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat. Acta Histochem 116(8):1289–1300. https://doi.org/10.1016/j.acthis.2014.07.012 CrossRefPubMedGoogle Scholar
- 32.Johnson AC, Tremble SM, Chan SL, Moseley J, LaMarca B, Nagle KJ, Cipolla MJ (2014) Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia. PLoS ONE 9(11):e113670. https://doi.org/10.1371/journal.pone.0113670 CrossRefPubMedPubMedCentralGoogle Scholar