Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis

Ferreira, Raphaela Costa; Fragoso, Marilene Brandão Tenório; Bueno, Nassib Bezerra; Goulart, Marília Oliveira Fonseca; Oliveira, Alane Cabral Menezes de

doi:10.1016/j.placenta.2020.07.023

Cited by 18 publications

(9 citation statements)

References 61 publications

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“…The placenta is also normally exposed to cycles of reduced and restored blood flow during uterine contractions before and during labor (Alotaibi et al, 2015;Brar et al, 1988), similar to the hypoxia-reperfusion associated with ferroptosis in the brain, kidneys and other organs (Friedmann Angeli et al, 2014;Schoots et al, 2018;Wenzel et al, 2017). This type of injury has been implicated in the placental dysfunction underlying fetal growth restriction, preeclampsia and related conditions (Burton and Jauniaux, 2018;Hung et al, 2002;Soleymanlou et al, 2005;Ferreira et al, 2020;Myatt, 2010). Together, these data highlight the relevance of trophoblast ferroptosis and macroblebbing to placental ferroptotic damage and common obstetrical disease.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis induces membrane blebbing in placental trophoblasts

Kajiwara

Beharier

Chng

et al. 2021

Journal of Cell Science

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Ferroptosis is a regulated, non-apoptotic form of cell death, characterized by hydroxy-peroxidation of discrete phospholipid hydroperoxides, particularly hydroperoxyl (Hp)- forms of arachidonoyl- and adrenoyl-phosphatidylethanolamine, with a downstream cascade of oxidative damage to membrane lipids, proteins, and DNA, culminating in cell death. We recently showed that human trophoblasts are particularly sensitive to ferroptosis, caused by depletion or inhibition of glutathione peroxidase 4 (GPX4) or the lipase PLA2G6. Here, we show that trophoblastic ferroptosis is accompanied by a dramatic change in trophoblast plasma membrane, with macro-blebbing and vesiculation. Immunofluorescence revealed that ferroptotic cell-derived blebs stained positive for F-actin, but negative for cytoplasmic organelle markers. Transfer of conditioned medium that contained detached macrovesicles or co-culture with blebbing cells did not stimulate ferroptosis in target cells. Molecular modeling showed that the presence of Hp- phosphatidylethanolamine in the cell membrane promoted its stretchability. Together, our data establish that membrane macro-blebbing is characteristic of trophoblast ferroptosis and can serve as a useful marker of this process. Whether or not these blebs are physiologically functional remains to be established.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis induces membrane blebbing in placental trophoblasts

Kajiwara

Beharier

Chng

et al. 2021

Journal of Cell Science

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“…Previous studies have shown that the activities of SOD and GPx are decreased, while MDA is increased in PE rat blood samples, suggesting the association of PE with OS 32 . A systematic review with meta‐analysis showed that OS existed in the preeclamptic placentas, and the results also showed that the activities of some enzymes (SOD and GPx) in the antioxidant system decreased, and markers of oxidative damage (MDA, lipid peroxidation) increased 33 . Our results showed that curcumin or aspirin treatment alleviated OS by increasing the production and activity of antioxidant SOD and reducing the secretion of pro‐oxidant MDA in serum and placenta of PE rats, proving the antioxidant property of curcumin or aspirin, further confirming the anti‐PE effect of curcumin or aspirin.…”

Section: Discussionmentioning

confidence: 94%

Combining curcumin and aspirin ameliorates preeclampsia‐like symptoms by inhibiting the placental TLR4/NF‐κB signaling pathway in rats

Feng

Yang

et al. 2022

J of Obstet and Gynaecol

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Aim: Preeclampsia (PE) is a common medical complication of pregnancy characterized by high blood pressure and proteinuria after the 20th gestational week. This study aimed to investigate the potency of the combination of curcumin and aspirin in the treatment of PE and explore the underlying mechanisms. Material and Methods: The PE model was constructed in female rats by administering 0.5 mg/mL N-nitro-L-arginine methyl ester from gestational days (GDs) 6 to 16. The pregnant female rats were divided into five groups according to the drug treatment. The curcumin or aspirin was given to the rats by tail vein injection (0.36 mg/kg) or gavage treatment (1.5 mg/kg BW/day) from GD4 to GD18. Results: Treatment with curcumin and aspirin combination significantly reduced the systolic blood pressure and proteinuria in the PE rats. Meanwhile, in comparison to the PE rats treated with single-dose curcumin or aspirin, the rats treated with combined curcumin and aspirin showed significantly decreased sFlt-1, increased placental growth factor, and alleviated oxidative stress in both blood and placental tissues, which are abnormal in no-treated PE rats. Furthermore, dramatically decreased inflammatory cytokines secretion and TLR4 and NF-κB p65 expression in placental tissues were also observed in the PE rats with combined treatment compared to those of no-treated, signal-dose curcumin or aspirin-treated PE rats. Conclusions: Our results suggested that the combined treatment of curcumin and aspirin significantly ameliorates the symptoms of PE in rats, which is most likely due to the inhibition of the placental TLR4/NF-κB p65 signaling pathway.

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“…It is widely speculated in the literature that preeclampsia, as well as hypertension during pregnancy, is associated with an imbalance of the placental antioxidant defence, composed of the enzymatic and nonenzymatic defence systems and, therefore, with increased ROS synthesis in the placenta [3,16,17]. Available research provides studies that the concentration of malondialdehyde measured in umbilical cord blood was a reliant marker of perinatal oxidative stress [18,19].…”

Section: Discussionmentioning

confidence: 99%

Malondialdehyde and Neutrophil Gelatinase-Associated Lipocalin as Markers of Oxidative Stress in Small for Gestational Age Newborns from Hypertensive and Preeclamptic Pregnancies

Surmiak

Wojnarowicz

Szymkowiak

2022

BioMed Research International

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Introduction. It is speculated that preeclampsia and hypertension during pregnancy are associated with an imbalance of the placental antioxidant defence, which results in the overproduction of reactive oxygen species and fetal growth restriction. Many research implied that oxidant stress in utero may be an important determinant of mortality and morbidity in neonates. Moreover, the authors demonstrated the reduced number of nephrons and a higher prevalence of renal injury in neonates with growth restriction, including small for gestational age (SGA) neonates. Alas, it remains unclear whether basal antioxidant status is altered in the kidneys of SGA newborns. Materials and Methods. In this study, we assessed neutrophil gelatinase-associated lipocalin (NGAL) and malondialdehyde (MDA) levels in samples collected from umbilical blood and 12 hours after delivery in neonates born by mothers suffering from preeclampsia or hypertension during pregnancy and those from physiological pregnancies. Additionally, the authors evaluated levels of the aforementioned biomarkers regarding the occurrence of growth restriction in newborns. For this study, we enrolled 27 newborns, which fulfilled inclusion criteria for SGA diagnosis (SGA group), while 21 were appropriate for gestational age neonates, as the AGA group. Results. In the presented study, we have found significant differences in umbilical cord MDA and NGAL concentration between the SGA and AGA groups. Such dependencies were not found in blood samples from neonates collected in the first 12 hours of life for MDA and NGAL concentrations. Additionally, we have observed differences in umbilical MDA and NGAL levels between newborns of preeclamptic or hypertensive mothers compared to healthy ones. A significant correlation between the occurrence of hypertension during pregnancy and umbilical MDA and NGAL concentrations was also found. Conclusions. Small for gestational age newborns or those born by preeclamptic and hypertensive mothers had significantly higher MDA and NGAL levels as compared to healthy ones. Further investigation is needed to understand the pathophysiologic influence of hypertension in pregnancy and oxidative stress injury in newborns with growth restriction.

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Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis

Cited by 18 publications

References 61 publications

Ferroptosis induces membrane blebbing in placental trophoblasts

Ferroptosis induces membrane blebbing in placental trophoblasts

Combining curcumin and aspirin ameliorates preeclampsia‐like symptoms by inhibiting the placental TLR4/NF‐κB signaling pathway in rats

Malondialdehyde and Neutrophil Gelatinase-Associated Lipocalin as Markers of Oxidative Stress in Small for Gestational Age Newborns from Hypertensive and Preeclamptic Pregnancies

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