Antioxidants

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10 pages, 308 KiB

Open AccessArticle

Elevation of Pulmonary Artery Pressure in Newborns from High-Altitude Pregnancies Complicated by Preeclampsia

by Carlos E. Salinas-Salmon, Carla Murillo-Jauregui, Marcelino Gonzales-Isidro, Vannia Espinoza-Pinto, Silvia V. Mendoza, Rosario Ruiz, Ronald Vargas, Yuri Perez, Jaime Montaño, Lilian Toledo, Abraham Badner, Jesús Jimenez, Javier Peñaranda, Catherine Romero, Martha Aguilar, Loyola Riveros-Gonzales, Ivar Arana and Eduardo Villamor

Antioxidants 2023, 12(2), 347; https://doi.org/10.3390/antiox12020347 - 1 Feb 2023

Cited by 2 | Viewed by 1955

Abstract

We hypothesized that fetal exposure to the oxidative stress induced by the combined challenge of preeclampsia (PE) and high altitude would induce a significant impairment in the development of pulmonary circulation. We conducted a prospective study in La Paz (Bolivia, mean altitude 3625 [...] Read more.

We hypothesized that fetal exposure to the oxidative stress induced by the combined challenge of preeclampsia (PE) and high altitude would induce a significant impairment in the development of pulmonary circulation. We conducted a prospective study in La Paz (Bolivia, mean altitude 3625 m) in which newborns from singleton pregnancies with and without PE were compared (PE group n = 69, control n = 70). We conducted an echocardiographic study in these infants at the median age of two days. The percentage of cesarean deliveries and small for gestational age (SGA) infants was significantly higher in the PE group. Heart rate, respiratory rate, and oxygen saturation did not vary significantly between groups. Estimated pulmonary arterial pressure and pulmonary vascular resistance were 30% higher in newborns exposed to PE and high altitude compared with those exposed only to high altitude. We also detected signs of right ventricular hypertrophy in infants subjected to both exposures. In conclusion, this study provides evidence that the combination of PE and pregnancy at high altitude induces subclinical alterations in the pulmonary circulation of the newborn. Follow-up of this cohort may provide us with valuable information on the potential increased susceptibility to developing pulmonary hypertension or other pulmonary and cardiovascular disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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17 pages, 2467 KiB

Open AccessArticle

Oleuropein Attenuates Oxidative Stress in Human Trophoblast Cells

by Andrea Pirković, Aleksandra Vilotić, Sunčica Borozan, Mirjana Nacka-Aleksić, Žanka Bojić-Trbojević, Milica Jovanović Krivokuća, Maurizio Battino, Francesca Giampieri and Dragana Dekanski

Antioxidants 2023, 12(1), 197; https://doi.org/10.3390/antiox12010197 - 14 Jan 2023

Cited by 6 | Viewed by 2724

Abstract

Olive-derived bioactive compound oleuropein was evaluated against damage induced by hydrogen peroxide in human trophoblast cells in vitro, by examining the changes in several markers implicated in oxidative stress interactions in the placenta. Trophoblast HTR-8/SVneo cells were preincubated with OLE at 10 [...] Read more.

Olive-derived bioactive compound oleuropein was evaluated against damage induced by hydrogen peroxide in human trophoblast cells in vitro, by examining the changes in several markers implicated in oxidative stress interactions in the placenta. Trophoblast HTR-8/SVneo cells were preincubated with OLE at 10 and 100 µM and exposed to H₂O₂, as a model of oxidative stress. Protein and lipid peroxidation, as well as antioxidant enzymes’ activity, were determined spectrophotometrically, and DNA damage was evaluated by comet assay. iNOS protein expression was assessed by Western blot, while the mRNA expression of pro- and anti-apoptotic genes BAX and BCL2 and transcription factor NFE2L2, as well as cytokines IL-6 and TNF α were determined by qPCR. Oleuropein demonstrated cytoprotective effects against H₂O₂ in trophoblast cells by significantly improving the antioxidant status and preventing protein and lipid damage, as well as reducing the iNOS levels. OLE reduced the mRNA expression of IL-6 and TNF α, however, it did not influence the expression of NFE2L2 or the BAX/BCL2 ratio after H₂O₂ exposure. Oleuropein per se did not lead to any adverse effects in HTR-8/SVneo cells under the described conditions, confirming its safety in vitro. In conclusion, it significantly attenuated oxidative damage and restored antioxidant functioning, confirming its protective role in trophoblast. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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15 pages, 2379 KiB

Open AccessArticle

Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction

by Natasha de Alwis, Sally Beard, Natalie K. Binder, Natasha Pritchard, Tu’uhevaha J. Kaitu’u-Lino, Susan P. Walker, Owen Stock, Katie Groom, Scott Petersen, Amanda Henry, Joanne M. Said, Sean Seeho, Stefan C. Kane, Stephen Tong, Lisa Hui and Natalie J. Hannan

Antioxidants 2022, 11(9), 1677; https://doi.org/10.3390/antiox11091677 - 27 Aug 2022

Cited by 1 | Viewed by 2867

Abstract

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to [...] Read more.

Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of both fetal growth restriction and preeclampsia, we aimed to investigate OLAH levels and function in the human placenta. We assessed OLAH mRNA expression (qPCR) throughout pregnancy, finding placental expression increased as gestation progressed. OLAH mRNA and protein levels (Western blot) were elevated in placental tissue from cases of preterm preeclampsia, while OLAH protein levels in placenta from growth-restricted pregnancies were comparatively reduced in the preeclamptic cohort. OLAH expression was also elevated in placental explant tissue, but not isolated primary cytotrophoblast cultured under hypoxic conditions (as models of placental dysfunction). Further, we discovered that silencing cytotrophoblast OLAH reduced the expression of pro- and anti-apoptosis genes, BAX and BCL2, placental growth gene, IGF2, and oxidative stress gene, NOX4. Collectively, these findings suggest OLAH could play a role in placental dysfunction and may be a therapeutic target for mitigating diseases associated with this vital organ. Further research is required to establish the role of OLAH in the placenta, and whether these changes may be a maternal adaptation or consequence of disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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26 pages, 5504 KiB

Open AccessArticle

Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance

by Jing Long, Yan Huang, Zhengshan Tang, Yali Shan, Dou Feng, Wenqin Wang, Juan Liu, Ying Huang, Hang Gu, Dewei Guo, Ruojin Yao and Xin Ni

Antioxidants 2022, 11(8), 1505; https://doi.org/10.3390/antiox11081505 - 31 Jul 2022

Cited by 10 | Viewed by 2649

Abstract

We have previously demonstrated that placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) dysfunction contributes to PE pathogenesis. We sought to elucidate molecular mechanisms underlying 11β-HSD2 dysfunction-induced PE and to seek potential therapeutic targets using a 11β-HSD2 dysfunction-induced PE-like rat model as well as cultured [...] Read more.

We have previously demonstrated that placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) dysfunction contributes to PE pathogenesis. We sought to elucidate molecular mechanisms underlying 11β-HSD2 dysfunction-induced PE and to seek potential therapeutic targets using a 11β-HSD2 dysfunction-induced PE-like rat model as well as cultured extravillous trophoblasts (EVTs) since PE begins with impaired function of EVTs. In 11β-HSD2 dysfunction-induced PE-like rat model, we revealed that placental mitochondrial dysfunction occurred, which was associated with mitDNA instability and impaired mitochondrial dynamics, such as decreased optic atrophy 1 (OPA1) expression. MitoTEMPO treatment significantly alleviated the hallmark of PE-like features and improved mitDNA stability and mitochondrial dynamics in the placentas of rat PE-like model. In cultured human EVTs, we found that 11β-HSD2 dysfunction led to mitochondrial dysfunction and disrupted mtDNA stability. MitoTEMPO treatment improved impaired invasion and migration induced by 11β-HSD2 dysfunction in cultured EVTs. Further, we revealed that OPA1 was one of the key factors that mediated 11β-HSD2 dysfunction-induced excess ROS production, mitochondrial dysfunction and mtDNA reduction. Our data indicates that 11β-HSD2 dysfunction causes mitochondrial dysfunctions, which impairs trophoblast function and subsequently results in PE development. Our study immediately highlights that excess ROS is a potential therapeutic target for PE. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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18 pages, 1976 KiB

Open AccessArticle

Lycopene Supplementation to Serum-Free Maturation Medium Improves In Vitro Bovine Embryo Development and Quality and Modulates Embryonic Transcriptomic Profile

by Shehu Sidi, Osvaldo Bogado Pascottini, Daniel Angel-Velez, Nima Azari-Dolatabad, Krishna Chaitanya Pavani, Gretania Residiwati, Tim Meese, Filip Van Nieuwerburgh, Elias Kambai Bawa, Ambrose Alikidon Voh, Joseph Olusegun Ayo and Ann Van Soom

Antioxidants 2022, 11(2), 344; https://doi.org/10.3390/antiox11020344 - 10 Feb 2022

Cited by 13 | Viewed by 3989

Abstract

Bovine embryos are typically cultured at reduced oxygen tension to lower the impact of oxidative stress on embryo development. However, oocyte in vitro maturation (IVM) is performed at atmospheric oxygen tension since low oxygen during maturation has a negative impact on oocyte developmental [...] Read more.

Bovine embryos are typically cultured at reduced oxygen tension to lower the impact of oxidative stress on embryo development. However, oocyte in vitro maturation (IVM) is performed at atmospheric oxygen tension since low oxygen during maturation has a negative impact on oocyte developmental competence. Lycopene, a carotenoid, acts as a powerful antioxidant and may protect the oocyte against oxidative stress during maturation at atmospheric oxygen conditions. Here, we assessed the effect of adding 0.2 μM lycopene (antioxidant), 5 μM menadione (pro-oxidant), and their combination on the generation of reactive oxygen species (ROS) in matured oocytes and the subsequent development, quality, and transcriptome of the blastocysts in a bovine in vitro model. ROS fluorescent intensity in matured oocytes was significantly lower in the lycopene group, and the resulting embryos showed a significantly higher blastocyst rate on day 8 and a lower apoptotic cell ratio than all other groups. Transcriptomic analysis disclosed a total of 296 differentially expressed genes (Benjamini–Hochberg-adjusted p < 0.05 and ≥ 1-log2-fold change) between the lycopene and control groups, where pathways associated with cellular function, metabolism, DNA repair, and anti-apoptosis were upregulated in the lycopene group. Lycopene supplementation to serum-free maturation medium neutralized excess ROS during maturation, enhanced blastocyst development and quality, and modulated the transcriptomic landscape. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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Review

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19 pages, 6462 KiB

Open AccessReview

The Importance of Natural Antioxidants in Female Reproduction

by Janka Vašková, Zuzana Klepcová, Ivana Špaková, Peter Urdzík, Jana Štofilová, Izabela Bertková, Marek Kľoc and Miroslava Rabajdová

Antioxidants 2023, 12(4), 907; https://doi.org/10.3390/antiox12040907 - 11 Apr 2023

Cited by 25 | Viewed by 9736

Abstract

Oxidative stress (OS) has an important role in female reproduction, whether it is ovulation, endometrium decidualization, menstruation, oocyte fertilization, or development andimplantation of an embryo in the uterus. The menstrual cycle is regulated by the physiological concentration of reactive forms of oxygen and [...] Read more.

Oxidative stress (OS) has an important role in female reproduction, whether it is ovulation, endometrium decidualization, menstruation, oocyte fertilization, or development andimplantation of an embryo in the uterus. The menstrual cycle is regulated by the physiological concentration of reactive forms of oxygen and nitrogen as redox signal molecules, which trigger and regulate the length of individual phases of the menstrual cycle. It has been suggested that the decline in female fertility is modulated by pathological OS. The pathological excess of OS compared to antioxidants triggers many disorders of female reproduction which could lead to gynecological diseases and to infertility. Therefore, antioxidants are crucial for proper female reproductive function. They play a part in the metabolism of oocytes; in endometrium maturation via the activation of antioxidant signaling pathways Nrf2 and NF-κB; and in the hormonal regulation of vascular action. Antioxidants can directly scavenge radicals and act as a cofactor of highly valuable enzymes of cell differentiation and development, or enhance the activity of antioxidant enzymes. Compensation for low levels of antioxidants through their supplementation can improve fertility. This review considers the role of selected vitamins, flavonoids, peptides, and trace elements with antioxidant effects in female reproduction mechanisms. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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23 pages, 1814 KiB

Open AccessReview

Antioxidants in Pregnancy: Do We Really Need More Trials?

by Carolina Di Fabrizio, Veronica Giorgione, Asma Khalil and Colin E. Murdoch

Antioxidants 2022, 11(5), 812; https://doi.org/10.3390/antiox11050812 - 22 Apr 2022

Cited by 10 | Viewed by 5313

Abstract

Human pregnancy can be affected by numerous pathologies, from those which are mild and reversible to others which are life-threatening. Among these, gestational diabetes mellitus and hypertensive disorders of pregnancy with subsequent consequences stand out. Health problems experienced by women during pregnancy and [...] Read more.

Human pregnancy can be affected by numerous pathologies, from those which are mild and reversible to others which are life-threatening. Among these, gestational diabetes mellitus and hypertensive disorders of pregnancy with subsequent consequences stand out. Health problems experienced by women during pregnancy and postpartum are associated with significant costs to health systems worldwide and contribute largely to maternal mortality and morbidity. Major risk factors for mothers include obesity, advanced maternal age, cardiovascular dysfunction, and endothelial damage; in these scenarios, oxidative stress plays a major role. Markers of oxidative stress can be measured in patients with preeclampsia, foetal growth restriction, and gestational diabetes mellitus, even before their clinical onset. In consequence, antioxidant supplements have been proposed as a possible therapy; however, results derived from large scale randomised clinical trials have been disappointing as no positive effects were demonstrated. This review focuses on the latest evidence on oxidative stress in pregnancy complications, their early diagnosis, and possible therapies to prevent or treat these pathologies. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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24 pages, 3367 KiB

Open AccessReview

Computational Models on Pathological Redox Signalling Driven by Pregnancy: A Review

by Samprikta Manna, Camino S. M. Ruano, Jana-Charlotte Hegenbarth, Daniel Vaiman, Shailendra Gupta, Fergus P. McCarthy, Céline Méhats, Cathal McCarthy, Clara Apicella and Julia Scheel

Antioxidants 2022, 11(3), 585; https://doi.org/10.3390/antiox11030585 - 18 Mar 2022

Cited by 4 | Viewed by 3964

Abstract

Oxidative stress is associated with a myriad of diseases including pregnancy pathologies with long-term cardiovascular repercussions for both the mother and baby. Aberrant redox signalling coupled with deficient antioxidant defence leads to chronic molecular impairment. Abnormal placentation has been considered the primary source [...] Read more.

Oxidative stress is associated with a myriad of diseases including pregnancy pathologies with long-term cardiovascular repercussions for both the mother and baby. Aberrant redox signalling coupled with deficient antioxidant defence leads to chronic molecular impairment. Abnormal placentation has been considered the primary source for reactive species; however, placental dysfunction has been deemed secondary to maternal cardiovascular maladaptation in pregnancy. While various therapeutic interventions, aimed at combating deregulated oxidative stress during pregnancy have shown promise in experimental models, they often result as inconclusive or detrimental in clinical trials, warranting the need for further research to identify candidates. The strengths and limitations of current experimental methods in redox research are discussed. Assessment of redox status and oxidative stress in experimental models and in clinical practice remains challenging; the state-of-the-art of computational models in this field is presented in this review, comparing static and dynamic models which provide functional information such as protein-protein interactions, as well as the impact of changes in molecular species on the redox-status of the system, respectively. Enhanced knowledge of redox biology in during pregnancy through computational modelling such as generation of Systems Biology Markup Language model which integrates existing models to a larger network in the context of placenta physiology. Full article

(This article belongs to the Special Issue Oxidative Stress in Reproduction)

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