Increased hepcidin levels in preeclampsia: a protective mechanism against iron overload mediated oxidative stress?

Abstract

Background

Pregnancy is a metabolic state which demands increased iron bioavailability. While in preeclampsia, due to the placental vascular events there is an iron surplus environment along with inflammation and placental hypoxia. Routinely in India iron is supplemented to all pregnant women irrespective of their general physical condition. Hepcidin a regulator of iron metabolism protects the cells from iron mediated cytotoxicity.

Objective

To find out whether hepcidin gets induced as a protective mechanism in preeclampsia patients in order to combat the environment of iron overload, oxidative stress, and endothelial dysfunction.

Methods

A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients in the gestational age 32 ± 4 weeks were recruited (n = 80). Biochemical analysis to assess the serum levels of the following were carried out (1) indices of iron homeostasis – serum iron, ferritin, transferrin, hepcidin, (2) endothelial dysfunction –serum assymetric dimethyl arginine (ADMA) (3) oxidative stress – Malon di aldehyde (MDA) and ferric reducing ability of plasma (FRAP). Kolmogorov-Smirnov test, Mann-Whitney U test, Spearman’s correlation, linear regression and ROC^AUC analysis were performed to understand their relationship with each other.

Results

Levels of serum iron, ferritin, transferrin saturation, hepcidin, and MDA/FRAP ratio were elevated significantly in preeclampsia patients compared to controls, while serum transferrin levels were significantly decreased in them. Hepcidin levels showed a significant positive correlation with serum ADMA, and MDA/FRAP. Serum hepcidin, transferrin saturationand MDA/FRAP ratio is useful in differentiating pre-eclampsia patients from healthy pregnant women.

Conclusion

Iron supplementation in preeclampsia patients might have led to a state of iron overload, which might have caused oxidative stress and endothelial dysfunction in preeclampsia patients. The rise in hepcidin levels in this scenario may be viewed as a protective mechanism to combat the iron overload mediated cytotoxicity.

Keywords:

• Hepcidin
• preeclampsia
• iron overload
• oxidative stress
• endothelial dysfunction

Disclosure statement

The authors declare that they have no conflict of interest related to the publication of this article.

Additional information

Funding

We are grateful to Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India for providing financial assistance in the form of an intramural research grant [Order No: JIP/Res/MD-MS/03/2015-16.]