Accumulation of Advanced Glycation End Products in Women with Preeclampsia: Possible Involvement of Placental Oxidative and Nitrative Stress

Abstract

Advanced glycation end products (AGEs) are known to cause oxidative damage in various cells by binding with its receptor, RAGE. We measured the serum level of AGEs and examined the AGEs, RAGE, and the other biomarkers of oxidative stress in the placentas from preeclamptic women. Competitive ELISA was carried out to measure the AGEs in serum. Western blotting was performed to analyze AGEs and RAGE in the placenta. Immunohistochemical analyses were performed to examine the localization of AGEs, RAGE, and other biomarkers of oxidative stress in the placenta. The mean level of serum AGEs in preeclamptic women was significantly higher than that in healthy non-pregnant women or healthy pregnant women. Western blotting revealed that the level of AGEs or RAGE in preeclamptic placenta was significantly higher than that in normal placenta. Immunohistochemical analyses showed that levels of nitrotyrosine and nitroguanosine, which are formed by reactive nitrogen species, in preeclamptic placenta were higher than those in normal placenta. Accumulation of 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine indicated enhanced oxidative modifications of lipids and DNA in preeclamptic placenta. The AGE-RAGE system, which is upregulated in preeclampsia, is likely to be involved in the oxidative stress of preeclampsia.

Sterile inflammation and pregnancy complications: a review

“…This finding was corroborated in a study by Zhu et al, with further evidence revealing increased levels of HMGB1 and RAGE in the placenta of women with severe PE, especially in the cytoplasmic compartment of trophoblasts (Zhu et al 2015). Additionally, RAGE and TLR4, two receptors with affinity for HMGB1, were found to have higher expression in placentas from pregnancies complicated with PE (Kim et al 2005, Chekir et al 2006. Pro-inflammatory effects of HMGB1 via TLR9 have been suggested to contribute to the pathophysiology of PE (Scharfe-Nugent et al 2012).…”

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism

“…In diabetes, there is evidence both in men and in animal models, whether spontaneously occurring (O'Neill et al 2009) or chemically induced diabetic mice (Shrilatha & Muralidhara 2007a, O'Neill et al 2009) and rats (Shrilatha & Muralidhara 2007b), that the condition is associated with marked increases in oxidative stress and sperm nDNA damage. Hyperglycaemia is known to cause oxidative stress (Wautier & Schmidt 2004, Chekir et al 2006 and to accelerate the accumulation of advanced glycation end products and their receptor RAGE, both of which are capable of generating, promoting and/or amplifying oxidative stress and its detrimental consequences. It is this amplification and extension of the injurious oxidative environment that may be responsible for the damage seen in the previously mentioned studies.…”

Study of the relationship between AGEs and oxidative stress damage to trophoblast cell mitochondria

“…This study also shows that mitochondrial oxidative stress damage in the AGEs group was significantly greater when compared to the group without AGEs. The expression of AGEs in maternal serum and in the placenta of the patients with pre-eclampsia was significantly higher when compared to the expression during normal pregnancy [1]. These observations suggest that AGEs maybe participate in the pathophysiology of pre-eclampsia by increasing oxidative stress damage.…”

“…Gueds et al [10] have also shown that the accumulation of AGEs can cause oxidative stress in the placenta and placental vascular dysfunction, and thus lead to pre-eclampsia. Chekir et al [1] found that expression of AGEs in maternal serum and in the placenta of patients with pre-eclampsia was significantly higher when compared to the expression during normal pregnancy, and markers of oxidative stress damage in the placenta were significantly increased. Such results could suggest that high expression of AGEs may have as important a role in the pathophysiology of pre-eclampsia as oxidative stress; although the exact mechanism is still unknown.…”

“…Chekir et al [1] have found that the expression of AGEs in maternal serum and placenta of patients with pre-eclampsia was significantly higher when compared to the expression in a normal pregnancy. However, the exact mechanisms responsible for pre-eclampsia are not completely understood.…”