Oxidative stress and preeclampsia

Abstract

Preeclampsia is a common disorder of human pregnancy and is a leading cause of maternal and neonatal death world-wide. The disease is polymorphic, with involvement of the placenta, maternal vasculature, central nervous system, coagulation cascade, liver and kidney. Preeclampsia is also associated with an increased incidence of fetal intrauterine growth restriction (IUGR). Often, the only treatment option is delivery with consequent fetal prematurity. The clinical markers of this disorder include hypertension and proteinuria, which reverse after delivery. Hypertension is a result of the disease and is rarely of pathogenic importance. When accompanied by convulsions the syndrome is termed eclampsia (derived from the Greek eklampsis or “sudden flashing”). A primary clinical goal is to prevent progression to this deadly complication. The incidence of preeclampsia is between 5 and 10% of pregnancies and there is no evidence that this has changed appreciably during the last century. Despite the lack of progress from a practical standpoint, new insights into the aetiology and pathogenesis of preeclampsia continue to arise.

A longitudinal study of biochemical markers of bone turnover during normal pregnancy and pregnancies complicated by pre-eclampsia

“…Thus increased bone metabolism in pre-eclampsia may be another facet of the multisystem involvement of the disease that occurs in response to circulating factor(s) released during the development of pre-eclampsia. Pre-eclampsia is associated with generalised endothelial cell dysfunction 14 , increased oxidative stress 15 , increased circulating levels of pro-inflammatory cytokines 16 and insulin-like growth factor binding protein-1 (IGFBP-1) 17 . Evidence from animal studies suggests that the increased circulating IGFBP-1 may be able to inhibit IGF-1-mediated bone formation 18 , while reactive oxygen species 19 , interleukin-6 and tumour necrosis factor-a (TNF-a) 20 stimulate osteoclast activity leading to bone resorption.…”

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia

“…There is clear evidence that pre-eclampsia is associated with endothelial cell dysfunction [4], possibly induced by oxidative stress [27]. The role of oxidative stress was investigated in a double-blind, randomized controlled trial of antioxidants (vitamin C and vitamin E) in women at increased risk of developing pre-eclampsia [28].…”

Hypertension in pregnancy

“…These include cytokines, TNF␣ in particular, 77 activated neutrophils, monocytes or platelets, 78 stable products of lipid peroxidation, 79 syncytiotrophoblast fragments and antibodies. The antibodies suggested include autoantibodies to endothelial cells 80 and more specifically autoantibodies to the angiotensin (AT 1 ) receptor 44 that are capable of activating the receptor.…”

“…There are increased concentrations of stable metabolites of the reactive lipid peroxides, malondialdehyde and isoprostanes in blood and tissues. 79 In addition, plasma from women with PE oxidizes ascorbic acid in vitro. Not surprisingly, circulating concentrations of this lynchpin antioxidant are reduced in women with PE, likely indicating consumption in vivo.…”