Abstract 2039: Urinary 8-Hydroxy-2′-Deoxyguanosine Levels Decrease After Cardioversion in Atrial Fibrillation

Background : Atrial fibrillation (AF) has been shown to be associated with increased oxidative stress mediated by reactive oxygen species (ROS). Previous studies have proposed that there is a link between oxidative stress and AF, and thus oxidative stress may contribute to the pathological consequences of AF such as thrombosis, inflammation, and atrial tissue remodeling. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) which is a product of deoxyribonucleic acid (DNA) damage by ROS has become to be regarded as a putative biomarker of oxidative DNA damage. Also, biopyrrins which are oxdative metabolites of bilirubin (an important scavenger of ROS) are considered as the potential marker of oxdative stress. In the present study, we assessed serial changes in oxidative stress in patients with AF after cardioversion by measuring urinary 8-OHdG and urinary biopyrrin excretion. Methods and Results : The study subjects consisted of 15 patients with persistent or chronic AF, who underwent electrical or pharmacological cardioversion. We measured urinary 8-OHdG and biopyrrin levels obtained before cardioversion and 24 hours after cardioversion using enzyme-linked immunosorbent assay. There was no significant difference in the biopyrrin/creatinine levels before and 24 hours after cardioversion (3.2±2.6 vs. 3.3±2.4 mU/mg, P=NS). However, 8-OHdG/creatinine levels decreased significantly 24 hours after cardioversion (18.4±9.1 vs. 14.7±8.5 ng/mg, P=0.0012). There was no significant correlation between urinary 8-OHdG/creatinine and biopyrrin/creatinine levels. This discrepancy may be related to the difference in the time course between urinary 8-OHdG/creatinine and biopyrrin/creatinine levels. Thus, measurement of 8-OHdG/creatinine levels seemed to be a more useful marker which reflects the oxidative stress than biopyrrin/creatinine levels at the time 24 hours after cardioversion. Conclusions : These findings suggest that the restoration of sinus rhythm by cardioversion decreases oxidative DNA damage in AF patients, and urinary 8-OHdG may be useful for the estimation of oxidative stress in AF patients. The increase of oxidative stress may play an important role in the pathogenesis of AF, and persist AF and result in the perpetuation of AF.

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ANALYSIS OF OXIDATIVE STRESS MARKERS MALONDIALDEHYDE, GLUTATHIONE, NITRIC OXIDE, AND PRORENIN LEVEL IN PREECLAMPSIA PLACENTAL TISSUES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v11i1.18330 ◽

2018 ◽

Vol 11 (1) ◽

pp. 158

Author(s):

Ani Retno Prijanti ◽

Nelly Marissa ◽

Reni Paramita ◽

Sarah Humaira ◽

Eldesta Nisa Nabila ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Late Onset ◽

Colorimetric Assay ◽

Vascular Wall ◽

Enzyme Linked Immunosorbent Assay ◽

No Production ◽

Spiral Artery ◽

Significant Difference ◽

The Difference

Objective: Preeclampsia was a syndrome of hypertension proteinuria in pregnant women. In failure of pseudo vasculogenesis, there is persistency of endothelial and smooth muscle cell of vessel wall in spiral artery. Spiral artery could not be emphasis and lead to relative hypoxia, and oxidative stress in placental tissues. Endothelial cell has property to produce nitric oxide (NO) that can dilated vessel. Placenta also produces prorenin, to maintain vascular wall tonicity. Therefore, we want to uncover the property of placenta is there any capacity of prorenin, is that prorenin could overcome the NO level, or is there any depression of NO production, and any oxidative stress.Methods: This observational study was used case–control design. We search preeclampsia cases during September-December 2015. We used preeclampsia placentas from early and late onset. We collect preeclampsia placentas from Cipto Mangunkusumo and normal placentas from Budi Kemuliaan Hospital. We used 30 preeclampsia placentas and 30 normal placentas. Markers measured were NO and prorenin. NO was measured using colorimetric assay kit (K262-200/ BioVision), and prorenin was measured using human prorenin enzyme-linked immunosorbent assay kit (ab157525/ Abcam). Glutathione (GSH) was measured using Ellman method and malondialdehyde (MDA) using Wills method.Results: Prorenin concentration between normal and preeclampsia placenta was analyzed using Mann–Whitney and show that there had no significant difference between preeclampsia and normal placentas (p=0.23). Besides, NO data analyzed using independent t-test show significant differences between preeclampsia and normal placentas (p=0.001). The difference between normal and preeclampsia GSH concentration was not significant (p=0.757), besides the difference between normal and preeclampsia MDA concentration was significant (p=0.000).Conclusion: NO concentration in preeclampsia placenta was increase, higher than normal placenta. There was no effect of preeclampsia on prorenin concentration and GSH. There was marked decrease of MDA in preeclampsia placentas.

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MEASUREMENT OF DNA DAMAGE, OXIDATIVE STRESS, AND GENE EXPRESSION OF β-CATENIN AND P53 GENES IN LIVER AND BRAIN OF MALE MICE RECEIVING MONOSODIUM L-GLUTAMATE MONOHYDRATE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i7.36019 ◽

2020 ◽

pp. 127-132

Author(s):

NOHA IBRAHIM SAID SALEM ◽

HANAN R.H. MOHAMED ◽

AREEG MOHAMED ABD-ELRAZEK

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Quantitative Polymerase Chain Reaction ◽

Significant Decline ◽

Control Group ◽

Group I ◽

Significant Difference ◽

P53 Genes

Introduction: Monosodium L-glutamate (MSG) monohydrate is a widespread nutritional additive and flavoring agent frequently consumed all over the world. In this study, we investigate the action of daily oral intake of MSG monohydrate in vivo using mammalian systems. Methods: Mice divided as follows: Group I (normal control), Group II, and Group III treated with MSG for 2 and 4 weeks, respectively. Brain and liver dissected out for the detection of fragmented DNA, DNA damage, and assay of oxidative stress markers. Moreover, expression levels of ß-Cat and p53 genes were measured by a real-time quantitative polymerase chain reaction. Results: The results showed a significant difference in MSG-treated group at the 2-time intervals than the control one regarding parameters of oxidative stress, and these were accompanied by a significant decline in glutathione (GSH) and a ratio of oxidized and reduced GSH in both tissues. Significant elevation of laddered DNA and oxidative DNA damage was observed in groups treated with MSG. In addition, a significant decline in gene expression of ß-Catenin in liver and brain tissues with elevations in the gene expression of p53 in the brain. Furthermore, the p53 gene in liver tissue was significantly upregulated in mice administered MSG for 15 days and was downregulated after 30 days of MSG intake compared with the control. Conclusion: According to our results, oral consumption of MSG leads to oxidative stress-mediated DNA damage and apoptosis.

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ANALYSIS OF OXIDATIVE STRESS MARKERS MALONDIALDEHYDE, GLUTATHIONE, NITRIC OXIDE, AND PRORENIN LEVEL IN PREECLAMPSIA PLACENTAL TISSUES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i1.18330 ◽

2018 ◽

Vol 11 (1) ◽

pp. 158

Author(s):

Ani Retno Prijanti ◽

Nelly Marissa ◽

Reni Paramita ◽

Sarah Humaira ◽

Eldesta Nisa Nabila ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Late Onset ◽

Colorimetric Assay ◽

Vascular Wall ◽

Enzyme Linked Immunosorbent Assay ◽

No Production ◽

Spiral Artery ◽

Significant Difference ◽

The Difference

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Effect of Coal Dust Exposure on the SOD Activity and the Oxidative DNA Damage in Asthmatic Mice

The Indonesian Biomedical Journal ◽

10.18585/inabj.v11i2.579 ◽

2019 ◽

Vol 11 (2) ◽

pp. 159-66

Author(s):

Windy Yuliana Budianto ◽

Husnul Khotimah ◽

Eko Suhartono

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Coal Dust ◽

Negative Control ◽

Dust Exposure ◽

Dust Particles ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Sod Activity

BACKGROUND: Coal dust is known to trigger hypersensitivity and inflammation of the respiratory tract as it increases oxidative stress leading to asthma. To date, the relationship of coal dust exposure in the pathomechanism of asthma remains unclear. This study was aimed to examine the effect of coal dust exposure on the superoxide dismutase (SOD) activity and the oxidative DNA damage indicated by increased serum 8-hydroxy-2' -deoxyguanosine (8-OHdG) in asthmatic mice.METHODS: Twenty-four female balb/c mice were divided into four groups. The first group was the control group. The second group was the negative control group which composed of mice exposed to coal dust particles. The third group was composed of ovalbumin (OVA)-sensitized mice. The fourth group was composed of OVA-sensitized mice and exposed to coal dust particles. The inflammatory process was identified by serum interleukin (IL)-13 concentration using Enzyme-linked Immunosorbent Assay (ELISA) method. Meanwhile, the oxidative stress was examined by measuring the SOD activity using the Nitro Blue Tetrazolium (NBT) method, and the 8-OHdG concentration was quantified by ELISA method.RESULTS: There was an increasing IL-13 in OVAtreated coal dust exposed group along with the increment of 8-OHdG (statistically not significant). SOD activity measured in serum was decreased in all groups (p>0.05). Combination of OVA and coal dust showed the worst effect on IL-13, 8-OHdG and SOD activity.CONCLUSION: Coal dust exposure for four weeks does not adequately induce the oxidative DNA damage in asthmatic mice.KEYWORDS: asthma, coal dust, IL-13, SOD, 8-OHdG

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Increased Plasma Levels of 8-Hydroxy-2′-deoxyguanosine (8-OHdG) in Patients with Pseudoexfoliation Glaucoma

Journal of Ophthalmology ◽

10.1155/2019/8319563 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Altaf A. Kondkar ◽

Tahira Sultan ◽

Taif A. Azad ◽

Lubna Tabussum ◽

Essam A. Osman ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Plasma Levels ◽

Oxidative Dna Damage ◽

Enzyme Linked Immunosorbent Assay ◽

Pseudoexfoliation Glaucoma ◽

Characteristic Analysis ◽

Retrospective Case ◽

Increased Risk ◽

The Mean

Purpose. To investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk. Materials and Methods. A retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing. Results. The mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11–14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518–0.751). Conclusion. The study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.

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Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-9-783-784 ◽

2020 ◽

pp. 783-783

Author(s):

I. A. Umnyagina ◽

L. A. Strakhova ◽

T. V. Blinova

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Blood Serum ◽

Oxidative Dna Damage ◽

Working Environment ◽

Working Environments ◽

Potential Biomarker ◽

High Level ◽

Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

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Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents

International Journal of Obesity ◽

10.1038/s41366-021-00879-2 ◽

2021 ◽

Author(s):

Moonisah Usman ◽

Maria Woloshynowych ◽

Jessica Carrilho Britto ◽

Ivona Bilkevic ◽

Bethany Glassar ◽

...

Keyword(s):

Vitamin D ◽

Dna Damage ◽

Genomic Instability ◽

Oxidative Dna Damage ◽

Nutritional Deficiencies ◽

Aetiological Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Childhood And Adolescence ◽

Paediatric Obesity ◽

Vitamin D Levels

Abstract Background/objectives Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status. Subjects/methods We carried out a cross-sectional study with 132 participants, aged 10–18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2′-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay. Results As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability. Conclusions Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures.

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Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress & Vascular Remodeling

Circulation ◽

10.1161/circ.118.suppl_18.s_302-d ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Marion Hofmann Bowman ◽

Jeannine Wilk ◽

Gene Kim ◽

Yanmin Zhang ◽

Jalees Rehman ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Smooth Muscle ◽

Vascular Remodeling ◽

Oxidative Dna Damage ◽

Fold Increase ◽

Brdu Incorporation ◽

Elastic Fibers ◽

Nuclear Staining

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p <0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p< 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p<0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.

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ID: 140: KLOTHO, AN ANTI-AGING MOLECULE, REGULATES ALVEOLAR EPITHELIAL CELL MTDNA DAMAGE AND APOPTOSIS

Journal of Investigative Medicine ◽

10.1136/jim-2016-000120.102 ◽

2016 ◽

Vol 64 (4) ◽

pp. 961.1-961

Author(s):

S Kim ◽

P Cheresh ◽

RP Jablonski ◽

DW Kamp ◽

M Eren ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Epithelial Cell ◽

Pulmonary Fibrosis ◽

Oxidative Dna Damage ◽

Alveolar Epithelial Cell ◽

Premature Aging ◽

Protective Effects ◽

Mtdna Damage ◽

Alveolar Epithelial

RationaleConvincing evidence has emerged that impaired alveolar epithelial cell (AEC) injury and repair resulting from ‘exaggerated’ lung aging and mitochondrial dysfunction are critical determinants of the lung fibrogenic potential of toxic agents, including asbestos fibers, but the mechanisms underlying these findings is unknown. We showed that the extent of AEC mitochondrial DNA (mtDNA) damage and apoptosis are critical determinants of asbestos-induced pulmonary fibrosis (Cheresh et al AJRCMB 2014, Kim et al JBC 2014). Klotho is an age-inhibiting gene and Klotho-deficient mice demonstrate a premature aging phenotype that includes a reduced lifespan, arteriosclerosis, and lung oxidative DNA damage, and that Klotho attenuates hyperoxic-induced AEC DNA damage and apoptosis (Ravikumar et al AJP-Lung 2014). We reason that Klotho has an important role in limiting pulmonary fibrosis by protecting the AECs from oxidative stress.MethodsQuantitative PCR-based measurement of mtDNA damage was assessed following transient transfection with wild-type Klotho, Klotho siRNA or AKT siRNA in A549 and/or MLE-12 cells for 48 hrs followed by exposure to either amosite asbestos (25 µg/cm2) or H2O2 (200 µM) for 24 hrs. Apoptosis was assessed by cleaved caspase-9/3 levels and DNA fragmentation assay. Murine pulmonary fibrosis was analyzed in male 8–10 week old WT (C3H/C57B6J) mice or Klotho heterozygous knockout (Kl+/−) mice following intratracheal instillation of a single dose of 100 µg crocidolite asbestos or titanium dioxide (negative control) using histology (fibrosis score by Masson's trichrome staining) and lung collagen (Sircoll assay).ResultsCompared to control, amosite asbestos or H2O2 reduces Klotho mRNA/protein expression. Notably, silencing of Klotho promotes oxidative stress-induced AEC mtDNA damage and apoptosis whereas Klotho-enforced expression (EE) and Euk-134, a mitochondrial ROS scavenger, are protective. Interestingly, Kl+/− mice have increased asbestos-induced lung fibrosis. Also, we find that inhibition or silencing of AKT augments oxidant-induced AEC mtDNA damage and apoptosis.ConclusionsOur data demonstrate a crucial role for AEC AKT signaling in mediating the mtDNA damage protective effects of Klotho. Given the importance of AEC aging and apoptosis in pulmonary fibrosis, we reason that Klotho/AKT axis is an innovative therapeutic target for preventing common lung diseases of aging (i.e. IPF, COPD, lung cancer, etc.) for which more effective management regimens are clearly needed.FundingNIH-RO1 ES020357-01A1 (DK) and VA Merit (DK).

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Small molecule inhibitor of OGG1 blocks oxidative DNA damage repair at telomeres and potentiates Methotrexate anticancer effects

10.21203/rs.3.rs-57290/v2 ◽

2020 ◽

Author(s):

Juan Miguel Baquero ◽

Carlos Benítez-Buelga ◽

Varshni Rajagopal ◽

Zhao Zhenjun ◽

Raúl Torres-Ruiz ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Cell Lines ◽

Small Molecule ◽

Oxidative Dna Damage ◽

Genome Instability ◽

Excision Repair ◽

Small Molecule Inhibitor ◽

Osteosarcoma Cell ◽

Molecule Inhibitor

Abstract Background: The most common oxidative DNA lesion is 8-oxoguanine (8-oxoG) which is mainly recognized and excised by the glycosylase OGG1, initiating the Base Excision Repair (BER) pathway. Telomeres are particularly sensitive to oxidative stress which disrupts telomere homeostasis triggering genome instability. Methods: We used U2OS OGG1-GFP osteosarcoma cell line to study the role of OGG1 at the telomeres in response to oxidative stress. Next, we investigated the effects of inactivating pharmacologically the BER during oxidative stress (OS) conditions by using a specific small molecule inhibitor of OGG1 (TH5487) in different human cell lines. Results: We have found that during OS, TH5487 effectively blocks BER initiation at telomeres causing accumulation of oxidized bases at this region, correlating with other phenotypes such as telomere losses, micronuclei formation and mild proliferation defects. Besides, the antimetabolite Methotrexate synergizes with TH5487 through induction of intracellular ROS formation, which potentiates TH5487 mediated telomere and genome instability in different cell lines. Conclusions: Our findings demonstrate that OGG1 is required to protect telomeres from OS and present OGG1 inhibitors as a tool to induce oxidative DNA damage at telomeres, with the potential for developing new combination therapies for cancer treatment.

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