Clinical Investigation
Alterations in Lipid Profile, Zinc and Copper Levels and Superoxide Dismutase Activities in Normal Pregnancy and Preeclampsia,☆☆

https://doi.org/10.1016/j.amjms.2017.03.022Get rights and content

Abstract

Background

Increased oxidative stress (OS) and lipid peroxidation may be involved in the pathogenesis of preeclampsia (PE). We conducted a case-control study to evaluate the levels of plasma lipids and trace elements as well as activity of superoxide dismutase (SOD) in PE.

Materials and Methods

The study consisted of 100 patients who had been diagnosed with PE and 100 normotensive pregnant women who underwent medical checkups that served as the control group. Lipid profile, zinc (Zn) and copper (Cu) levels and SOD activities were measured in the plasma of all subjects.

Results

Our results showed that the plasma levels of triglycerides and SOD activity were significantly elevated and the levels of Zn and Cu were significantly reduced in patients with PE compared with healthy controls. Increased levels of SOD may indicate antioxidant protective mechanisms against OS in PE-complicated pregnancies. This finding may suggest an involvement of OS in the pathophysiology of PE.

Conclusion

This study demonstrated a significant negative correlation between SOD activity and levels of trace elements. Furthermore, we suggest that higher triglyceride levels and SOD activity combined with lower Zn and Cu levels may be associated with an increased risk of PE.

Introduction

Preeclampsia (PE) is a serious complication that occurs during the second and third trimester of pregnancy and affects the health of both the mother and fetus.1 It is a rapidly progressive condition characterized by proteinuria, hypertension and edema.2 Despite advances in the management of PE, it is still the main cause of maternal and perinatal mortality, complicating 5-10% of pregnancies worldwide.3 In Iran, the prevalence of PE was reported to be 1-8% of pregnancies.4

Although the etiology and pathogenesis of PE remain undefined, the occurrence of oxidative stress (OS) is a feature of this disease.5, 6, 7 However, there are controversial reports regarding the serum levels of antioxidant enzymes. For instance, Ilhan et al6 reported that superoxide dismutase (SOD) levels were reduced in the serum of patients with PE. However, Sharma et al5 showed an increase in serum SOD levels in patients with PE compared to a control group. Furthermore, another study demonstrated that there was no significant difference in the serum levels of antioxidant enzymes, such as catalase and SOD, between the control and PE groups.8

SODs are a family of metalloenzymes that catalyze the conversion of superoxide radical (O2•−) to oxygen (O2) and hydrogen peroxide (H2O2). Therefore, they are involved in cellular protection against the toxicity caused by OS.9, 10 These enzymes carry out catalysis via a general mechanism that involves the sequential reduction and oxidation of the metals such as manganese (MnSOD in mitochondria and peroxisomes), copper and zinc (CuZnSOD in the cytosol and in the extracellular space).11 Because of the biological role of these metals in endogenous antioxidant enzymes, some studies have evaluated the serum levels of these elements, and controversial results have been reported. Several authors show decreased or unchanged levels of these elements,12, 13, 14 while others demonstrate increased levels of trace elements.6, 15, 16

Furthermore, the association of alteration of serum lipid profile in PE is well documented. Lipid alterations may lead to a reduction in the prostacyclin-thromboxane A2 (PGI2/TXA2) ratio. The altered prostaglandin ratio might stimulate increased lipid peroxidation and promote OS in PE.17 Race and ethnicity play an important role in the development of PE, and so far, no studies have been performed on zinc (Zn) and copper (Cu) combined with related antioxidant enzymes, such as SOD, in Iranian pregnant women with PE. Therefore, we decided to conduct a study in this field.

The aim of this study was to assess lipid profile status and the antioxidative systems in PE by measuring plasma Zn and Cu levels and SOD activities in pregnant women with or without PE.

Section snippets

Population Study

The case-control study was carried out at Qaem, Imam Reza and Omollbanin hospitals in Mashhad, Iran, from June 2014-May 2015. A total of 200 subjects (100 women with PE (PE group) and 100 normotensive pregnant women (control group), ages 16-42 years) were included in this study. Selected patients and healthy volunteers were matched for age and gestation age.

PE was defined as proteinuria (1+ on dipstick urinalysis or higher), hypertension (140/90 mm Hg or higher) and edema during the second and

Results

The PE group and control group were well matched for age and gestation age. Weight and BMI were significantly different between the groups (P < 0.001).

The PE group had significantly higher systolic and diastolic blood pressure compared to the control group (P < 0.001) (Table 1). In the PE group, urinalysis showed 65% at the 1+ level, 28% at the 2+ level and 7% at the 3+ level whereas all controls were nil or trace. History of PE in a previous pregnancy was 1% and 43% in control group and PE

Discussion

PE is a complication during pregnancy, which may threaten the life of both mother and fetus.1 Many studies have divulged that OS plays a main role in the initiation and development of many vascular disorders, including atherosclerosis, hypertension and so forth.21, 22 This study was conducted based on the hypothesis that OS may play a major role in the development of PE. In this study, we evaluated the concentration of plasma lipid profile levels (TC, TG, LDL-C and HDL-C), Zn and Cu along with

Conclusion

This study reports on lipid profile, Zn and Cu status and SOD activity in preeclamptic women as compared with normotensive pregnant women. Our results show the levels of TG and HDL-C to be significantly higher as well as the levels of Zn and Cu to be significantly lower in plasma of patients with PE compared with controls. Additionally, enhanced SOD activity was shown in patients with PE when compared to normotensive pregnant women. We suggest that the possible pathogenesis of PE is OS caused

References (74)

  • J.W. Gofman et al.

    The serum lipoprotein transport system in health, metabolic disorders, atherosclerosis and coronary heart disease

    J Clin Lipidol

    (2007)
  • D.R. Jones et al.

    Estrogen receptor-mediated repression of human hepatic lipase gene transcription

    J Lipid Res

    (2002)
  • J. Sharma et al.

    Oxidative stress markers and antioxidant levels in normal pregnancy and pre‐eclampsia

    Int J Gynecol Obstet

    (2006)
  • E. Llurba et al.

    A comprehensive study of oxidative stress and antioxidant status in preeclampsia and normal pregnancy

    Free Radic Biol Med

    (2004)
  • Y. Wang et al.

    Increased superoxide generation is associated with decreased superoxide dismutase activity and mRNA expression in placental trophoblast cells in pre-eclampsia

    Placenta

    (2001)
  • J. Chisolm et al.

    Zinc, cadmium, metallothionein, and progesterone: do they participate in the etiology of pregnancy induced hypertension?

    Med Hypotheses

    (1985)
  • T. Tamura et al.

    Maternal plasma zinc concentrations and pregnancy outcome

    Am J Clin Nutr

    (2000)
  • F.F. Cherry et al.

    Plasma zinc in hypertension/toxemia and other reproductive variables in adolescent pregnancy

    Am J Clin Nutr

    (1981)
  • B. Bassiouni et al.

    Maternal and fetal plasma zinc in pre-eclampsia

    Eur J Obstet Gynecol Reprod Biol

    (1979)
  • J.J. Kopelman et al.

    Plasma cortisol levels and cortisol binding in normal and pre-eclamptic pregnancies

    Am J Obstet Gynecol

    (1970)
  • A. Flynn et al.

    Rapid serum-zinc depletion associated with corticosteroid therapy

    Lancet

    (1971)
  • H. Sandstead et al.

    Current concepts on trace minerals. Clinical considerations

    Med Clin North Am

    (1970)
  • D.-M. Dai et al.

    Hematocrit and plasma albumin levels difference may be a potential biomarker to discriminate preeclampsia and eclampsia in patients with hypertensive disorders of pregnancy

    Clin Chim Acta

    (2017)
  • R. Henkin et al.

    Maternal-fetal metabolism of copper and zinc at term

    Am J Obstet Gynecol

    (1971)
  • Y. Atamer et al.

    Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia

    Eur J Obstetr Gynecol Reprod Biol

    (2005)
  • H.G. Orhan et al.

    Correlation between plasma malondialdehyde and ceruloplasmin activity values in preeclamptic pregnancies

    Clin Biochem

    (2001)
  • S. Guller et al.

    Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia

    Lab Investig

    (2008)
  • Y. Engin-Üstün et al.

    Maternal serum ceruloplasmin in preeclampsia

    Int J Gynecol Obstet

    (2005)
  • J. Sarkar et al.

    Role of ceruloplasmin in macrophage iron efflux during hypoxia

    J Biol Chem

    (2003)
  • L.K. Wagner

    Diagnosis and management of preeclampsia

    Am Fam Physician

    (2004)
  • M. Safary et al.

    Prevalence of pre-eclampsia and its correlated maternal and fetal complications, Emam Sajjad Hospital, Yasuj,2001

    Shahrekord Univ Med Sci J

    (2003)
  • C.A. Hubel

    Oxidative stress in the pathogenesis of preeclampsia

    Exp Biol Med

    (1999)
  • S. Nasrollahi et al.

    Antioxidant status and serum levels of selectins in pre-eclampsia

    J Obstet Gynaecol (Lahore)

    (2015)
  • I. Fridovich

    Superoxide radical and superoxide dismutases

    Annu Rev Biochem

    (1995)
  • P. Kiilholma et al.

    Copper and zinc in pre-eclampsia

    Acta Obstet Gynecol Scand

    (1984)
  • N. Al-Jameil et al.

    Correlation between serum trace elements and risk of preeclampsia: a case controlled study in Riyadh, Saudi Arabia

    Saudi J Biol Sci

    (2015)
  • Y. Ma et al.

    The relationship between serum zinc level and preeclampsia: a meta-analysis

    Nutrients

    (2015)
  • Cited by (33)

    • Association between trace elements and preeclampsia: A retrospective cohort study

      2022, Journal of Trace Elements in Medicine and Biology
      Citation Excerpt :

      Our findings showed that higher copper levels were associated with a lower preeclampsia risk, consistent with the results of earlier similar studies [30,31]. A case-control study reported that compared with healthy pregnant women, plasma levels of copper in women with preeclampsia were significantly reduced [32]. Similarly, Acikgoz, S also observed significantly low copper levels in preeclampsia patients, compared to healthy pregnant women [33].

    • Pregnancy-induced hypertension: Role of drug therapy and nutrition in the management of hypertension

      2021, PharmaNutrition
      Citation Excerpt :

      Thus, a physiological decrease in zinc levels can potentially impair the antioxidant capacity during pregnancy. Few studies have reported that deficiency of zinc, iron, copper, calcium, and magnesium is associated with an increased risk of preeclampsia [100–102]. However, clinical studies elucidating the significant role of zinc alone in the management of preeclampsia are still awaited.

    View all citing articles on Scopus

    Financial support: This work was supported financially by the grant from Mashhad University of Medical Science (grant number 921939).

    ☆☆

    The authors have no conflict of interest to disclose.

    View full text