Title: Antioxidants in Pre-eclampsia

Key words: Antioxidants, pregnancy, oxidative stress, clinical predictors,

Date: June 1999

Category: 13. Specific Conditions

Type: Article

Author: Dr van Rhijn

 

 

Antioxidants in Pre-eclampsia

Introduction

Pre-eclampsia is a systemic pregnancy syndrome, characterised by reduced uteroplacental blood flow, diffuse endothelial dysfunction, increased peripheral vascular resistance, hypertension, coagulation abnormalities, elevations of maternal leukocyte-derived cytokines, hyperlipidemia, proteinuria, and oedema. The hypotheses suggest reactive oxygen species or their metabolites (oxidative stress) ultimately compromise the "defensive" vasodilatory, anti-aggregatory, and barrier functioning of the vascular endothelium1 due to uncontrolled lipid oxidation.

Diminished Antioxidant Protection

Oxidative stress in the maternal compartment may be due to pre-existing factors (e.g., obesity, diabetes, hyperlipidemia) or caused by placental lipid peroxides. Decreased placental antioxidant enzyme protection is followed by a cascade of events of uncontrolled lipid peroxidation with increased thromboxane production, increased tumor necrosis factor (TNF-alpha) production, cytokine interleukin (IL-6, IL-8) and TNF-alpha, which are of monocytic origin2 and decreased prostacyclin3. Activated intervillous leucocytes serve as mediators linking increased placental oxidative stress with increased maternal oxidative stress and endothelial dysfunction. Antioxidant capacity in the third trimester (rapid placental growth) fails and leads to membrane instability, failure of foetal protection systems and clinical symptoms of preeclampsia4. Increased lipid peroxidation is correlated with hypertension and serum uric acid levels5, but not with clinical severity6. Shallow implantation, hypoxic maternal-fetal interface, and increased turnover of trophoblast tissue, result in higher hypoxanthine, xanthine concentrations and hyperuricemia characterize preeclampsia7.

Studies have confirmed the imbalance between increased lipid peroxidation (MDA) and reduced8, 9, 10 sera antioxidant activity [vitamin E11, C12, 13 & A14] in preeclampsia. Reduced plasma superoxide dismutase (CuZn-SOD)15 and glucose 6-phosphate-dehydrogenase16 levels and increased placenta activities of catalase17, glutathione-S-transferase and glutathione peroxidase (Gpx) were found in preeclampsia, associated with fetal growth retardation or asphyxia18.

Antioxidant Strategies
A 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia19. Higher levels of beta-carotene (0.5 - 1 mumol/L) inhibited peroxide-induced vasoconstriction and lipid peroxide and thromboxane secretion20, but results from antioxidant treatment with vitamin E21, vitamin C and allopurinol was not encouraging22. Low-dose aspirin in pre-eclamptic placentas inhibits lipid peroxides and thromboxane without affecting prostacyclin23. The oxidation of erythrocyte glutathione was inhibited by the presence of the cyclooxygenase inhibitor indomethacin, and may be of value in the treatment of oxidative pathologies24.

Clinical Predictors of Pre-eclampsia
Prediction of risk or identification of subclinical disease is desirable because of the lack of proven prophylaxis for preeclampsia.
Potential candidate markers would include:

Conclusion

Preeclampsia is associated with premature delivery, foetal growth retardation, increased maternal and neonatal morbidity and mortality. Prospective longitudinal studies are required to evaluate potential predictive markers useful for early identification and successful therapeutic antioxidative prevention27, as currently conducted in the Vitamins In Pre-eclampsia (VIP) study in London.

 

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