Radicals, Oxidative/Nitrosative Stress and Preeclampsia

Abstract

Preeclampsia (PE) has a profound effect in increasing both maternal and fetal morbidity and mortality especially in third World. Disturbances of extravillous trophoblast migration toward uterine spiral arteries is characteristic feature of PE, which, in turn, leads to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Underlying pathogenesis appeared to be an altered bioavailability of nitric oxide (NO•) and tissue damage caused by increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The increase in ROS and RNS production or the decrease in antioxidant mechanisms generates a condition called oxidative and nitrosative stress, respectively, defined as the imbalance between pro- and antioxidants in favor of the oxidants. Additionally, ROS might trigger platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. As a consequence of these disorders could result in deficiencies in oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the one hand, enzymatic and nonenzymatic antioxidants scavenge ROS and protect tissues against oxidative damage. More specifically, placental antioxidant enzymes including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) protect the vasculature from ROS, maintaining the vascular function. On the other hand, ischemia in placenta in PE reduces the antioxidant activity. Collectively, the extent of oxidative stress would increase and therefore leads to the development of the pathological findings of PE including hypertension and proteinuria. Our goal in this article is to review current literature about researches demonstrating the interplay between oxidative, nitrosative stresses and PE, about their roles in the pathophysiology of PE and also about the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation.

Keywords: Antioxidant; PE; free radicals; nitrosative stress; oxidative stress; preeclampsia..