Protective effects of Bioflavonoids and their metabolites against oxidative stress in transformed first trimester trophoblast cells

Oxidative stress is considered a key hallmark of preeclampsia, which causes the dysregulation of trophoblast cells, and it contributes to the pathogenesis of preeclampsia. Emerging evidence has suggested bromodomain-containing protein 4 (BRD4) as a key regulator of oxidative stress in multiple cell types. However, whether BRD4 participates in regulating oxidative stress in trophoblast cells remains undetermined. The current study was designed to explore the potential function of BRD4 in the regulation of oxidative stress in trophoblast cells. Our data revealed that BRD4 expression was elevated in trophoblast cells stimulated with hydrogen peroxide. Exposure to hydrogen peroxide caused marked decreases in the levels of proliferation and invasion but promoted apoptosis and the production of ROS in trophoblast cells. Knockdown of BRD4, or treatment with a BRD4 inhibitor, markedly increased the levels of cell proliferation and invasion and decreased apoptosis and ROS production following the hydrogen peroxide challenge. Further data indicated that suppression of BRD4 markedly decreased the expression levels of Keap1, but increased the nuclear expression of Nrf2 and enhanced Nrf2-mediated transcriptional activity. BRD4 inhibition-mediated protective effects were markedly reversed by Keap1 overexpression or Nrf2 inhibition. Overall, these results demonstrated that BRD4 inhibition attenuated hydrogen peroxide-induced oxidative stress injury in trophoblast cells by enhancing Nrf2 activation via the downregulation of Keap1. Our study highlights the potential importance of the BRD4/Keap1/Nrf2 axis in the modulation of the oxidative stress response in trophoblast cells. Targeted inhibition of BRD4 may offer new opportunities for the development of innovative therapeutic approaches to treat preeclampsia.

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Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts

BioMed Research International ◽

10.1155/2015/257090 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 31

Author(s):

Courtney E. Cross ◽

Mai F. Tolba ◽

Catherine M. Rondelli ◽

Meixiang Xu ◽

Sherif Z. Abdel-Rahman

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Mrna Expression ◽

Expression Profiles ◽

First Trimester ◽

Mirna Profile ◽

Trophoblast Cells ◽

Placental Development ◽

Short Term ◽

Short Term Exposure

The relationship between oxidative stress and miRNA changes in placenta as a potential mechanism involved in preeclampsia (PE) is not fully elucidated. We investigated the impact of oxidative stress on miRNAs and mRNA expression profiles of genes associated with PE in villous 3A first trimester trophoblast cells exposed to H2O2at 12 different concentrations (0-1 mM) for 0.5, 4, 24, and 48 h. Cytotoxicity, determined using the SRB assay, was used to calculate the IC50of H2O2. RNA was extracted after 4 h exposure to H2O2for miRNA and gene expression profiling. H2O2exerted a concentration- and time-dependent cytotoxicity on 3A trophoblast cells. Short-term exposure of 3A cells to low concentration of H2O2(5% of IC50) significantly altered miRNA profile as evidenced by significant changes in 195 out of 595 evaluable miRNAs. Tool for annotations of microRNAs (TAM) analysis indicated that these altered miRNAs fall into 43 clusters and 34 families, with 41 functions identified. Exposure to H2O2altered mRNA expression of 22 out of 84 key genes involved in dysregulation of placental development. In conclusion, short-term exposure of villous first trimester trophoblasts to low concentrations of H2O2significantly alters miRNA profile and expression of genes implicated in placental development.

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Effect of Selenium and Iodine on Oxidative Stress in the First Trimester Human Placenta Explants

Nutrients ◽

10.3390/nu13030800 ◽

2021 ◽

Vol 13 (3) ◽

pp. 800

Author(s):

Nahal Habibi ◽

Agatha Labrinidis ◽

Shalem Yiner-Lee Leemaqz ◽

Tanja Jankovic-Karasoulos ◽

Dylan McCullough ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Potassium Iodide ◽

Human Placenta ◽

Sodium Selenite ◽

First Trimester ◽

Antioxidant Systems ◽

Protective Effects ◽

High Concentration ◽

Icp Ms

Imbalanced maternal micronutrient status, poor placentation, and oxidative stress are associated with greater risk of pregnancy complications, which impact mother and offspring health. As selenium, iodine, and copper are essential micronutrients with key roles in antioxidant systems, this study investigated their potential protective effects on placenta against oxidative stress. First trimester human placenta explants were treated with different concentrations of selenium (sodium selenite), iodine (potassium iodide), their combination or copper (copper (II) sulfate). The concentrations represented deficient, physiological, or super physiological levels. Oxidative stress was induced by menadione or antimycin. Placenta explants were collected, fixed, processed, and embedded for laser ablation inductively coupled plasma-mass spectrometry (LA ICP-MS) element imaging or immunohistochemical labelling. LA ICP-MS showed that placenta could uptake selenium and copper from the media. Sodium selenite and potassium iodide reduced DNA damage and apoptosis (p < 0.05). Following oxidative stress induction, a higher concentration of sodium selenite (1.6 µM) was needed to reduce DNA damage and apoptosis while both concentrations of potassium iodide (0.5 and 1 µM) were protective (p < 0.05). A high concentration of copper (40 µM) increased apoptosis and DNA damage but this effect was no longer significant after induction of oxidative stress. Micronutrients supplementation can increase their content within the placenta and an optimal maternal micronutrient level is essential for placenta health.

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Effect of Oxidative Stress and Fatty Acids Disbalance on the Development of Apoptosis in the Placenta with Cytomegalovirus Infection in the First Trimester

Acta biomedica scientifica ◽

10.29413/abs.2019-4.2.2 ◽

2019 ◽

Vol 4 (2) ◽

pp. 16-22

Author(s):

N. A. Ishutina ◽

I. A. Andrievskaya ◽

I. V. Dovzhikova ◽

N. N. Dorofienko ◽

N. N. Gorikov

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Fatty Acid ◽

Phospholipase A2 ◽

Pregnant Women ◽

Peripheral Blood ◽

Catalase Activity ◽

Cytomegalovirus Infection ◽

First Trimester ◽

Trophoblast Cells

Background. Reactivation of cytomegalovirus infection (CMV) during pregnancy is associated with manifestation of oxidative stress, both in the maternal peripheral blood and in the placental tissues. One of the effects of oxidative stress is a disturbance of the metabolism of fatty acids, which leads to the initiation of the apoptotic cascade, the death of trophoblast cells and, as a result, tissue or organ dysfunction, promoting to the development of a pathological condition. However, an analysis of the current literature indicates insufficient information on this problem in the villous chorion of the placenta in CMV infection.Aims. To study the relationship between the oxidative stress development and fatty acid imbalance in apoptosis of trophoblast cells during reactivation of CMV in the first trimester.Material and methods. We examined peripheral blood, urine, a homogenate of the villous chorions from 35 pregnant women with CMV reactivation within 9–11 weeks of pregnancy and from 30 pregnant women without CMV of the same gestation period. We studied levels of IgM and IgG for cytomegalovirus, low-avid IgG antibodies to cytomegalovirus (avidity index), phospholipase A2 content, fatty acid content, number of apoptotic trophoblast cells, fatty acid peroxide content and catalase activity. Sampling and analysis of material from pregnant women was conducted in 2016–2018.Results. The reactivation of CMV in the first trimester of pregnancy led to an increase content in the phospholipase A2 in villous chorion by 2.5 times, by 1.5 times of fatty acid peroxides, 1.5 times arachidonic acid, palmitic acid by 1.3 times, number of trophoblast cells in a state of apoptosis by 4.7 times and decrease catalase activity by 1.44 times.Conclusion. As a result of the study, cytomegalovirus-dependent induction of oxidative stress and imbalance of fatty acids triggering apoptosis of trophoblast cells was identified. Increased apoptosis initiates inflammation and destructive processes in the early placenta.

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Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

Reproductive Sciences ◽

10.1177/1933719114557894 ◽

2014 ◽

Vol 22 (6) ◽

pp. 718-724 ◽

Cited By ~ 4

Author(s):

Jay M. Bolnick ◽

Brian A. Kilburn ◽

Alan D. Bolnick ◽

Michael P. Diamond ◽

Manvinder Singh ◽

...

Keyword(s):

Oxidative Stress ◽

First Trimester ◽

Trophoblast Cells

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Protective Effects of Chungkookjang Extract on High Glucose Induced Oxidative Stress in LLC-PK1Cells

Preventive Nutrition and Food Science ◽

10.3746/jfn.2008.13.2.084 ◽

2008 ◽

Vol 13 (2) ◽

pp. 84-89 ◽

Cited By ~ 2

Author(s):

Na-Ri Yi ◽

Kyoung-Chun Seo ◽

Ji-Myung Choi ◽

Eun-Ju Cho ◽

Young-Ok Song ◽

...

Keyword(s):

Oxidative Stress ◽

High Glucose ◽

Protective Effects

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Protective Effects of Perilla frutescens Britt var. japonica Extracts from Oxidative Stress in Human HaCaT Keratinocytes

Journal of the Korean Society of Food Science and Nutrition ◽

10.3746/jkfn.2013.42.2.161 ◽

2013 ◽

Vol 42 (2) ◽

pp. 161-167 ◽

Cited By ~ 3

Author(s):

Na Ji ◽

Jia-Le Song ◽

Jeung-Ha Kil ◽

Kun-Young Park

Keyword(s):

Oxidative Stress ◽

Perilla Frutescens ◽

Protective Effects ◽

Hacat Keratinocytes

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Protective effects of andrographolide derivative AL-1 on high glucose-induced oxidative stress in RIN-m cells

Current Pharmaceutical Design ◽

10.2174/1381612821666150921110716 ◽

2016 ◽

Vol 22 (4) ◽

pp. 499-505 ◽

Cited By ~ 9

Author(s):

Hui Yan ◽

Yongmei Li ◽

Yali Yang ◽

Zaijun Zhang ◽

Gaoxiao Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

High Glucose ◽

M Cells ◽

Protective Effects

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Effects of Montmorillonite on Growth Performance, Serum Biochemistry and Oxidative Stress of Red-Crowned Crane (Grus japonensis) Fed Mycotoxin-Contaminated Feed

Current Drug Metabolism ◽

10.2174/1389200221666200726221126 ◽

2020 ◽

Vol 21 (8) ◽

pp. 626-632 ◽

Cited By ~ 1

Author(s):

Dawei Liu ◽

Qinghua Wu ◽

Hongyi Liu ◽

Changhu Lu ◽

Chao Gu ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Performance ◽

Feed Intake ◽

Animal Feed ◽

Bird Species ◽

Serum Biochemistry ◽

Protective Effects ◽

Regular Diet ◽

Grus Japonensis ◽

And Oxidative Stress

Background: The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redcrowned crane’s regular diets in China. Objective: This experiment was conducted to investigate the protective effects of mycotoxin binder montmorillonite (Mont) on growth performance, serum biochemistry and oxidative stress parameters of the red-crowned crane. Methods: 16 red-crowned cranes were divided into four groups and fed one of the following diets; a selected diet, regular diet, or the selected diet or regular diet with 0.5% montmorillonite added to the diets. The cranes' parameters of performance, hematology, serum biochemistry and serum oxidative stress were measured. Results: Consuming regular diets decreased the average daily feed intake (ADFI), levels of haemoglobin (Hb), platelet count (PLT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), but increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK) and lactate dehydrogenase (LDH). The supplementation of 0.5% Mont provided protection for the red-crowned crane in terms of feed intake, serum biochemistry and oxidative stress. Moreover, Mont supplementation had no adverse effect on the health of red-crowned crane. Conclusions: Taken together, these findings suggested that the addition of dietary Mont is effective in improving the health of red-crowned crane.

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Protective Effects of GYY4137 on Renal Ischaemia/Reperfusion Injury through Nrf2-Mediated Antioxidant Defence

Kidney & Blood Pressure Research ◽

10.1159/000509933 ◽

2021 ◽

pp. 1-9

Author(s):

Hongmei Zhao ◽

Yun Qiu ◽

Yichen Wu ◽

Hong Sun ◽

Sumin Gao

Keyword(s):

Oxidative Stress ◽

Reperfusion Injury ◽

Nuclear Translocation ◽

Organ Damage ◽

Related Factor ◽

Protective Effects ◽

Ischaemia Reperfusion Injury ◽

Renal Ischaemia ◽

Ischaemia Reperfusion ◽

Renal Histology

Introduction/Aims: Hydrogen sulfide (H2S) is considered to be the third most important endogenous gasotransmitter in organisms. GYY4137 is a long-acting donor for H2S, a gas transmitter that has been shown to prevent multi-organ damage in animal studies. We previously reported the effect of GYY4137 on cardiac ischaemia reperfusion injury (IRI) in diabetic mice. However, the role and mechanism of GYY4137 in renal IRI are poorly understood. The aims of this study were to determine whether GYY4137 can effectively alleviate the injury induced by renal ischaemia reperfusion and to explore its possible mechanism. Methods: Mice received right nephrectomy and clipping of the left renal pedicle for 45 min. GYY4137 was administered by intraperitoneal injection for 2 consecutive days before the operation. The model of hypoxia/reoxygenation injury was established in HK-2 cells, which were pre-treated with or without GYY4137. Renal histology, function, apoptosis, and oxidative stress were measured. Western blot was used to measure the target protein after renal IRI. Results: The results indicated that GYY4137 had a clear protective effect on renal IRI as reflected by the attenuation of renal dysfunction, renal tubule injury, and apoptosis. Moreover, GYY4137 remarkably reduced renal IRI-induced oxidative stress. GYY4137 significantly elevated the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and the expression of antioxidant enzymes regulated by Nrf2, including SOD, HO-1, and NQO-1. Conclusions: GYY4137 alleviates ischaemia reperfusion-induced renal injury through activating the antioxidant effect mediated by Nrf2 signalling.

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