Effects of iron-related compounds and bilirubin on redox homeostasis in endometriosis and its malignant transformations

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hiroshi Shigetomi ◽  
Shogo Imanaka ◽  
Hiroshi Kobayashi
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Heme Iron ◽  
Total Iron ◽  
University Hospital ◽  
Free Iron ◽  
Significant Difference ◽  
Iron Heme ◽  
Related Compounds

Abstract Objectives The balance between oxidative stress and antioxidant defense has been reported to differ between women with endometriosis and patients with its malignant transformation. The aim of this study is to investigate changes in redox balance in endometriosis and endometriosis-related ovarian cancer (EAOC) by simultaneously measuring iron-related compounds and bilirubin. Methods This study included 235 patients with a histopathologically confirmed diagnosis of endometriosis (n=178) and EAOC (n=57). Cyst fluid samples were collected in Nara Medical University hospital from January 2013 to May 2019. The levels of iron-related compounds (total iron, heme iron, free iron, oxyhemoglobin [oxyHb], methemoglobin [metHb], and metHb/oxyHb ratio) and bilirubin were measured. Results Total iron, heme iron, free iron, metHb/oxyHb ratio, and bilirubin were significantly elevated in endometriosis compared to EAOC. In both endometriosis and EAOC, iron-related compounds in the cyst were correlated with each other. There was no statistically significant difference in oxyHb and metHb levels between the two groups, but the metHb/oxyHb ratio was significantly higher in endometriosis than in EAOC. Bilirubin was positively correlated with total iron and free iron in EAOC, but there was no correlation between bilirubin and iron-related compounds in endometriosis. Conclusions Iron-induced oxidative stress in endometriosis may exceed bilirubin-dependent antioxidant capability, while redox homeostasis in EAOC can be maintained by at least bilirubin.

scholarly journals ATM inhibition enhances Auranofin-induced oxidative stress and cell death in lung cell lines

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244060
Author(s):  
Vanessa Ehrenfeld ◽  
Jan R. Heusel ◽  
Simone Fulda ◽  
Sjoerd J. L. van Wijk
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Ataxia Telangiectasia ◽  
Redox Homeostasis ◽  
Thioredoxin Reductase ◽  
Redox Balance ◽  
Lung Cells ◽  
Chromosomal Breakage ◽  
Atm Kinase ◽  
Cellular Reactive Oxygen Species

Ataxia-Telangiectasia (A-T), a pleiotropic chromosomal breakage syndrome, is caused by the loss of the kinase Ataxia-telangiectasia mutated (ATM). ATM is not only involved in the response to DNA damage, but also in sensing and counteracting oxidative stress. Since a disturbed redox balance has been implicated in the pathophysiology of A-T lung disease, we aimed to further explore the interplay between ATM and oxidative stress in lung cells. Using a kinetic trapping approach, we could demonstrate an interaction between the trapping mutant TRX1-CS and ATM upon oxidative stress. We could further show that combined inhibition of thioredoxin reductase (TrxR) and ATM kinase activity, using Auranofin and KU55933 respectively, induced an increase in cellular reactive oxygen species (ROS) levels and protein oxidation in lung cells. Furthermore, ATM inhibition sensitized lung cells to Auranofin-induced cell death that could be rescued by ROS scavengers. As a consequence, targeted reduction of ATM by TRX1 could serve as a regulator of oxidative ATM activation and contribute to the maintenance of the cellular redox homeostasis. These results highlight the importance of the redox-active function of ATM in preventing ROS accumulation and cell death in lung cells.

scholarly journals Transcriptional regulators of redox balance and other homeostatic processes with the potential to alter neurodegenerative disease trajectory

2017 ◽  
Vol 45 (6) ◽  
pp. 1295-1303 ◽  
Author(s):  
Scott W. Burnside ◽  
Giles E. Hardingham
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disease ◽  
Glutamate Uptake ◽  
Redox Homeostasis ◽  
Neuronal Loss ◽  
Redox Balance ◽  
Antioxidant Defences ◽  
Disease Trajectory ◽  
Inflammatory Status ◽  
The Brain

Diverse neurodegenerative diseases share some common aspects to their pathology, with many showing evidence of disruption to the brain's numerous homeostatic processes. As such, imbalanced inflammatory status, glutamate dyshomeostasis, hypometabolism and oxidative stress are implicated in many disorders. That these pathological processes can influence each other both up- and downstream makes for a complicated picture, but means that successfully targeting one area may have an effect on others. This targeting requires an understanding of the mechanisms by which homeostasis is maintained during health, in order to uncover strategies to boost homeostasis in disease. A case in point is redox homeostasis, maintained by antioxidant defences co-ordinately regulated by the transcription factor Nrf2, and capable of preventing not only oxidative stress but also inflammation and neuronal loss in neurodegenerative disease models. The emergence of other master regulators of homeostatic processes in the brain controlling inflammation, mitochondrial biogenesis, glutamate uptake and energy metabolism raises the question as to whether they too can be targeted to alter disease trajectory.

scholarly journals Is There a Balance in Oxidative-Antioxidant Status in Blood Serum of Patients with Advanced Endometriosis?

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1097
Author(s):  
Izabela Kokot ◽  
Agnieszka Piwowar ◽  
Marcin Jędryka ◽  
Ewa Maria Kratz
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Total Bilirubin ◽  
Redox Homeostasis ◽  
Curve Analysis ◽  
Control Group ◽  
Roc Curve Analysis ◽  
Non Invasive ◽  
Gynecological Disorders ◽  
Significant Difference

Can redox homeostasis indicators be potential non-invasive markers, crucial in the diagnosis and treatment of endometriosis? We checked if the differences in levels of serum oxidative-antioxidant balance parameters (TAS, FRAP, albumin, total bilirubin, uric acid, iron, SIRT3, SIRT5, SIRT6, telomerase, AOPP) are significant between patients with advanced endometriosis (E), healthy women (control group, C) and non-endometriosis women, but with other gynecological disorders (NE). The FRAP concentrations were significantly higher in E and NE group than in the control group (p = 0.015 and p = 0.017, respectively). The telomerase concentrations were significantly higher in the endometriosis group than in the control group (p = 0.004). Significantly higher concentrations of AOPP were observed in E (p < 0.001) and NE groups (p = 0.028) in comparison to the control subjects. Between stages III and IV of endometriosis, a significant difference existed only in concentration of iron (p = 0.013). There were no significant differences between the studied groups in the values of the remaining parameters. Based on the results of ROC curve analysis, we can conclude that the levels of serum FRAP, telomerase and AOPP may be taken into account as promising diagnostics markers that reflect the degree of oxidative stress accompanying advanced endometriosis.

scholarly journals Parkinson Disease-Linked Parkin Mediates Redox Reactions That Lower Oxidative Stress In Mammalian Brain

2020 ◽  
Author(s):  
Daniel N. El Kodsi ◽  
Jacqueline M. Tokarew ◽  
Rajib Sengupta ◽  
Nathalie A. Lengacher ◽  
Andy C. Ng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reductase Activity ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Oxidative Modification ◽  
Reduced Form ◽  
Mammalian Brain ◽  
Anti Oxidant

SUMMARYWe recently hypothesized that parkin plays a role in redox homeostasis and provided evidence that it directly reduces hydrogen peroxide (H2O2) in vitro. Here, we examined this anti-oxidant activity in vivo. Informed by findings in human brain, we demonstrate that elevated oxidative stress promotes parkin insolubility in mice. In normal mouse brain parkin was partially oxidized, e.g., at cysteines 195 and 252, which was augmented by oxidative stress. Although under basal conditions H2O2 levels were unchanged in adult prkn-/- brain, a parkin-dependent reduction of cytosolic H2O2 was observed when mitochondria were impaired, either due to neurotoxicant exposure (MPTP) or Sod2 haploinsufficiency. In accordance, markers of oxidative stress, e.g., protein carbonylation and nitrotyrosination, were elevated in the cytosol but not in mitochondria from prkn-/- mice. Nevertheless, this rise in oxidative stress led to changes in mitochondrial enzyme activities and the metabolism of glutathione in cells and mammalian brain. In parkin’s absence reduced glutathione concentrations were increased including in human cortex. This compensation was not due to new glutathione synthesis but attributed to elevated oxidized glutathione (GSSG)-reductase activity. Moreover, we discovered that parkin also recycled GSSG to its reduced form. With this reaction, parkin became S-glutathionylated, e.g., at cysteines 59 and human-specific 95. This oxidative modification was reversed by glutaredoxin. Our results demonstrate that cytosolic parkin mediates anti-oxidant reactions including H2O2 reduction and glutathione regeneration. These reducing activities lead to a range of oxidative modifications in parkin itself. In parkin-deficient brain oxidative stress rises despite changes to maintain redox balance.

scholarly journals Regulation of redox balance using a biocompatible nanoplatform enhances phototherapy efficacy and suppresses tumor metastasis

2021 ◽  
Vol 12 (1) ◽  
pp. 148-157
Author(s):  
Qunying Jiang ◽  
Min Pan ◽  
Jialing Hu ◽  
Junlin Sun ◽  
Lei Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tumor Metastasis ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Primary Tumors ◽  
Highly Effective

Amplified oxidative stress achieved by modulating redox homeostasis with PDA–MB for highly effective synergistic phototherapy to inhibit primary tumors and metastases.

scholarly journals Airway Redox Homeostasis and Inflammation Gone Awry: From Molecular Pathogenesis to Emerging Therapeutics in Respiratory Pathology

2020 ◽  
Vol 21 (23) ◽  
pp. 9317
Author(s):  
Javier Checa ◽  
Josep M. Aran
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Structural Cell ◽  
Environmental Threats ◽  
Chronic Lung Diseases ◽  
Cell Components ◽  
Respiratory Pathology

As aerobic organisms, we are continuously and throughout our lifetime subjected to an oxidizing atmosphere and, most often, to environmental threats. The lung is the internal organ most highly exposed to this milieu. Therefore, it has evolved to confront both oxidative stress induced by reactive oxygen species (ROS) and a variety of pollutants, pathogens, and allergens that promote inflammation and can harm the airways to different degrees. Indeed, an excess of ROS, generated intrinsically or from external sources, can imprint direct damage to key structural cell components (nucleic acids, sugars, lipids, and proteins) and indirectly perturb ROS-mediated signaling in lung epithelia, impairing its homeostasis. These early events complemented with efficient recognition of pathogen- or damage-associated recognition patterns by the airway resident cells alert the immune system, which mounts an inflammatory response to remove the hazards, including collateral dead cells and cellular debris, in an attempt to return to homeostatic conditions. Thus, any major or chronic dysregulation of the redox balance, the air–liquid interface, or defects in epithelial proteins impairing mucociliary clearance or other defense systems may lead to airway damage. Here, we review our understanding of the key role of oxidative stress and inflammation in respiratory pathology, and extensively report current and future trends in antioxidant and anti-inflammatory treatments focusing on the following major acute and chronic lung diseases: acute lung injury/respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and cystic fibrosis.

scholarly journals The Effect of Selected Dental Materials Used in Conservative Dentistry, Endodontics, Surgery, and Orthodontics as Well as during the Periodontal Treatment on the Redox Balance in the Oral Cavity

2020 ◽  
Vol 21 (24) ◽  
pp. 9684
Author(s):  
Izabela Zieniewska ◽  
Mateusz Maciejczyk ◽  
Anna Zalewska
Keyword(s):  
Oxidative Stress ◽  
Oral Cavity ◽  
Dental Treatment ◽  
Cell Metabolism ◽  
Redox Homeostasis ◽  
Dental Materials ◽  
Redox Balance ◽  
Titanium Implants ◽  
Dental Composite ◽  
Root Canal Filling

Oxidative stress (OS) is a redox homeostasis disorder that results in oxidation of cell components and thus disturbs cell metabolism. OS is induced by numerous internal as well as external factors. According to recent studies, dental treatment may also be one of them. The aim of our work was to assess the effect of dental treatment on the redox balance of the oral cavity. We reviewed literature available in PubMed, Medline, and Scopus databases, including the results from 2010 to 2020. Publications were searched according to the keywords: oxidative stress and dental monomers; oxidative stress and amalgam; oxidative stress and periodontitis, oxidative stress and braces, oxidative stress and titanium; oxidative stress and dental implants, oxidative stress and endodontics treatment, oxidative stress and dental treatment; and oxidative stress and dental composite. It was found that dental treatment with the use of composites, amalgams, glass-ionomers, materials for root canal filling/rinsing, orthodontic braces (made of various metal alloys), titanium implants, or whitening agents can disturb oral redox homeostasis by affecting the antioxidant barrier and increasing oxidative damage to salivary proteins, lipids, and DNA. Abnormal saliva secretion/composition was also observed in dental patients in the course of OS. It is suggested that the addition of antioxidants to dental materials or antioxidant therapy applied during dental treatment could protect the patient against harmful effects of OS in the oral cavity.

scholarly journals Oxidative stress and adrenocortical insufficiency

2014 ◽  
Vol 221 (3) ◽  
pp. R63-R73 ◽  
Author(s):  
R Prasad ◽  
J C Kowalczyk ◽  
E Meimaridou ◽  
H L Storr ◽  
L A Metherell
Keyword(s):  
Oxidative Stress ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Cytochrome P450 Enzymes ◽  
Cellular Functions ◽  
Electron Leakage ◽  
Cell Dysfunction ◽  
Glutathione Peroxidases ◽  
Adrenal Steroidogenesis ◽  
Glucocorticoid Deficiency

Maintenance of redox balance is essential for normal cellular functions. Any perturbation in this balance due to increased reactive oxygen species (ROS) leads to oxidative stress and may lead to cell dysfunction/damage/death. Mitochondria are responsible for the majority of cellular ROS production secondary to electron leakage as a consequence of respiration. Furthermore, electron leakage by the cytochrome P450 enzymes may render steroidogenic tissues acutely vulnerable to redox imbalance. The adrenal cortex, in particular, is well supplied with both enzymatic (glutathione peroxidases and peroxiredoxins) and non-enzymatic (vitamins A, C and E) antioxidants to cope with this increased production of ROS due to steroidogenesis. Nonetheless oxidative stress is implicated in several potentially lethal adrenal disorders including X-linked adrenoleukodystrophy, triple A syndrome and most recently familial glucocorticoid deficiency. The finding of mutations in antioxidant defence genes in the latter two conditions highlights how disturbances in redox homeostasis may have an effect on adrenal steroidogenesis.

Food Frequency Questionnaire for Assessing Infant Iron Nutrition

2005 ◽  
Vol 66 (3) ◽  
pp. 176-182 ◽  
Author(s):  
Patricia L. Williams ◽  
Sheila M. Innis
Keyword(s):  
Vitamin C ◽  
Food Frequency Questionnaire ◽  
Iron Status ◽  
Heme Iron ◽  
Total Iron ◽  
Iron Nutrition ◽  
Deficiency Anemia ◽  
Food Record ◽  
Food Frequency ◽  
Iron Heme

A food frequency questionnaire (FFQ) was developed and tested for assessing iron nutrition in infants through comparison with a three-day food record (3d-FR) and measures of iron status. Parents of 148 infants aged eight to 26 months completed a 3d-FR and an FFQ. Blood was collected for measures of hemoglobin (Hgb), ferritin, and transferrin receptor (sTfR). Iron deficiency anemia and iron depletion (ferritin ≤12 µg/L) were found in 9% and 26% of infants, respectively. The intakes of energy, total iron, heme and non-heme iron, vitamin C, and dietary fibre determined by the FFQ were associated with the intakes of the same nutrient determined by the 3d-FR (p<0.05). The intakes of energy, total iron, non-heme and heme iron, vitamin C, and fibre were significantly higher when estimated by the FFQ than by the 3d-FR. Total and heme iron intakes determined by the FFQ were significantly associated with serum ferritin, sTfR, and the sTfR:ferritin ratio (p<0.05). However, iron intakes explained <10% of the variability in iron status. Despite relative validity of the FFQ for evaluating differences in energy, iron, vitamin C, and fibre intake compared with a 3d-FR, FFQs need further development before they can be used to advance assessment of iron intake and status in infants.

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