In vivo Oxidative DNA Damage and lipid Peroxidation as a Biomarker of Oxidative Stress in Preterm Low-Birthweight Infants

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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Concurrent Increase of Oxidative DNA Damage and Lipid Peroxidation Together with Mitochondrial DNA Mutation in Human Lung Tissues During Aging—Smoking Enhances Oxidative Stress on the Aged Tissues

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1998.1036 ◽

1999 ◽

Vol 362 (2) ◽

pp. 309-316 ◽

Cited By ~ 55

Author(s):

Hsin-Chen Lee ◽

Maria L.R. Lim ◽

Ching-You Lu ◽

Vincent W.S. Liu ◽

Huei-Jyh Fahn ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Dna Damage ◽

Mitochondrial Dna ◽

Oxidative Dna Damage ◽

Human Lung ◽

Mitochondrial Dna Mutation ◽

Dna Mutation

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Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress

Infection and Immunity ◽

10.1128/iai.00991-06 ◽

2006 ◽

Vol 74 (12) ◽

pp. 6839-6846 ◽

Cited By ~ 56

Author(s):

Ge Wang ◽

Yang Hong ◽

Adriana Olczak ◽

Susan E. Maier ◽

Robert J. Maier

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Wild Type Mouse ◽

Wild Type ◽

Oxygen Intermediates ◽

Physiological Analysis ◽

H Pylori

ABSTRACT Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

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Increased oxidative DNA damage, lipid peroxidation, and reactive oxygen species in cultured orbital fibroblasts from patients with Graves’ ophthalmopathy: evidence that oxidative stress has a role in this disorder

Eye ◽

10.1038/eye.2010.31 ◽

2010 ◽

Vol 24 (9) ◽

pp. 1520-1525 ◽

Cited By ~ 33

Author(s):

C-C Tsai ◽

S-B Wu ◽

C-Y Cheng ◽

S-C Kao ◽

H-C Kau ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Lipid Peroxidation ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Reactive Oxygen ◽

Oxygen Species ◽

Graves Ophthalmopathy ◽

Orbital Fibroblasts

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Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats

Developmental Neuroscience ◽

10.1159/000446276 ◽

2016 ◽

Vol 38 (2) ◽

pp. 150-162 ◽

Cited By ~ 11

Author(s):

Bhupesh Patel ◽

Saroj Kumar Das ◽

Manorama Patri

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Brain Development ◽

Early Adolescence ◽

Hippocampal Neurons ◽

Oxidative Dna Damage ◽

Specific Effect ◽

Adolescence Period

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2′-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats.

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DNA damage after long-term repetitive hyperbaric oxygen exposure

Journal of Applied Physiology ◽

10.1152/japplphysiol.90737.2008 ◽

2009 ◽

Vol 106 (1) ◽

pp. 311-315 ◽

Cited By ~ 19

Author(s):

Michael Gröger ◽

Sükrü Öter ◽

Vladislava Simkova ◽

Markus Bolten ◽

Andreas Koch ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Endurance Training ◽

Hyperbaric Oxygen ◽

Oxidative Dna Damage ◽

Ex Vivo ◽

Pure Oxygen ◽

Repetitive Exposure

A single exposure to hyperbaric oxygen (HBO), i.e., pure oxygen breathing at supra-atmospheric pressures, causes oxidative DNA damage in humans in vivo as well as in isolated lymphocytes of human volunteers. These DNA lesions, however, are rapidly repaired, and an adaptive protection is triggered against further oxidative stress caused by HBO exposure. Therefore, we tested the hypothesis that long-term repetitive exposure to HBO would modify the degree of DNA damage. Combat swimmers and underwater demolition team divers were investigated because their diving practice comprises repetitive long-term exposure to HBO over years. Nondiving volunteers with and without endurance training served as controls. In addition to the measurement of DNA damage in peripheral blood (comet assay), blood antioxidant enzyme activities, and the ratio of oxidized and reduced glutathione content, we assessed the DNA damage and superoxide anion radical (O2•−) production induced by a single ex vivo HBO exposure of isolated lymphocytes. All parameters of oxidative stress and antioxidative capacity in vivo were comparable in the four different groups. Exposure to HBO increased both the level of DNA damage and O2•− production in lymphocytes, and this response was significantly more pronounced in the cells obtained from the combat swimmers than in all the other groups. However, in all groups, DNA damage was completely removed within 1 h. We conclude that, at least in healthy volunteers with endurance training, long-term repetitive exposure to HBO does not modify the basal blood antioxidant capacity or the basal level of DNA strand breaks. The increased ex vivo HBO-related DNA damage in isolated lymphocytes from these subjects, however, may reflect enhanced susceptibility to oxidative DNA damage.

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Nonthermal Dielectric-Barrier Discharge Plasma-Induced Inactivation Involves Oxidative DNA Damage and Membrane Lipid Peroxidation inEscherichia coli

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01002-10 ◽

2011 ◽

Vol 55 (3) ◽

pp. 1053-1062 ◽

Cited By ~ 263

Author(s):

Suresh G. Joshi ◽

Moogega Cooper ◽

Adam Yost ◽

Michelle Paff ◽

Utku K. Ercan ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Dna Damage ◽

Dielectric Barrier Discharge ◽

Oxidative Dna Damage ◽

Barrier Discharge ◽

Membrane Lipid ◽

Membrane Lipid Peroxidation ◽

Dbd Plasma ◽

Dielectric Barrier

ABSTRACTOxidative stress leads to membrane lipid peroxidation, which yields products causing variable degrees of detrimental oxidative modifications in cells. Reactive oxygen species (ROS) are the key regulators in this process and induce lipid peroxidation inEscherichia coli. Application of nonthermal (cold) plasma is increasingly used for inactivation of surface contaminants. Recently, we reported a successful application of nonthermal plasma, using a floating-electrode dielectric-barrier discharge (FE-DBD) technique for rapid inactivation of bacterial contaminants in normal atmospheric air (S. G. Joshi et al., Am. J. Infect. Control 38:293-301, 2010). In the present report, we demonstrate that FE-DBD plasma-mediated inactivation involves membrane lipid peroxidation inE. coli. Dose-dependent ROS, such as singlet oxygen and hydrogen peroxide-like species generated during plasma-induced oxidative stress, were responsible for membrane lipid peroxidation, and ROS scavengers, such as α-tocopherol (vitamin E), were able to significantly inhibit the extent of lipid peroxidation and oxidative DNA damage. These findings indicate that this is a major mechanism involved in FE-DBD plasma-mediated inactivation of bacteria.

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Oxidative DNA damage and lipid peroxidation to cluster vs. traditional sets resistance exercise in professional volleyball players

Kinesiology ◽

10.26582/k.48.1.10 ◽

2016 ◽

Vol 48 (1) ◽

pp. 63-70

Author(s):

Hamid Arazi ◽

Mohsen Sahebi ◽

Abbas Asadi

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Dna Damage ◽

Uric Acid ◽

Resistance Exercise ◽

Oxidative Dna Damage ◽

Crossover Fashion ◽

Loading Pattern ◽

Loading Patterns ◽

Volleyball Players

Cells continuously produce free radicals and reactive oxygen species (ROS) as part of metabolic processes. Exercise can induce an imbalance between ROS and antioxidants, which is referred to as oxidative stress. Acute bout of resistance exercise (RE) induces activation of several distinct systems of radicals generation, but the effects of different RE loading on oxidative stress response is not clear. Therefore, the purpose of this study was to examine the influence of cluster vs. traditional sets of RE on oxidative DNA damage, lipid peroxidation and uric acid response in athletes. To elicit blood oxidative stress, 12 professional young male volleyball players undertook two different RE loading patterns: 1) cluster loading pattern, 2) traditional loading pattern which was standardized for total volume and completed in a randomized crossover fashion with a four-day interval between trials. Blood samples were collected before and after RE for markers of oxidative stress and damage. In response to both the cluster and traditional sets, 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), and uric acid were significantly elevated post exercise (p<.05). Although no statistically significant differences between loading patterns were observed, the rate of elevations in 8-OHdG (effect size [ES]: 1.4 vs. 1.3) and 4-HNE (ES: 8.1 vs. 7.9) was greater for the traditional sets; likewise, the rate of uric acid excretion was greater for the cluster RE (ES: 1.6 vs. 1.4). These data suggests that RE induced DNA damage, and lipid peroxidation, but they were greater for the traditional RE. Therefore, strength and conditioning professionals in the field of volleyball must keep in their mind that RE induces oxidative stress and should use proper RE loading patterns in their training schedule.

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Ameliorative Effect of Eugenol and Anethole on Arsenic Induced Oxidative DNA Damage in Cultured Human Peripheral Blood Lymphocytes

International Journal of Pharmaceutical Sciences and Drug Research ◽

10.25004/ijpsdr.2017.090306 ◽

2017 ◽

Vol 9 (3) ◽

Author(s):

Anita Yadav ◽

Surbhi Bal ◽

Neha Verma ◽

Neeraj K. Aggarwal ◽

Ranjan Gupta

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Dna Damage ◽

Peripheral Blood ◽

Oxidative Dna Damage ◽

Human Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Tail Moment ◽

Blood Lymphocytes ◽

Human Peripheral Blood Lymphocytes

Arsenic contamination is one of the major health concerns all over the world and associated with various types of cancer and pathological effects. The production of reactive oxygen species (ROS) plays a crucial role in arsenic mediated toxicity. Several studies have shown that population constantly exposed to arsenic have substantial oxidative stress that, in turn, induces DNA damage. In the present work eugenol and anethole were investigated for their protective effect against arsenic mediated oxidative DNA damage in peripheral blood lymphocytes. Comet assay and lipid peroxidation was used as biomarker of genotoxicity and oxidative stress respectively. A dose dependent increase in tail moment and lipid peroxidation was observed when lymphocytes were treated with sodium arsenite. Treatment of arsenic (50?M) along with eugenol (20?M) and anethole (50?M) showed a significant decrease in the tail moment and lipid peroxidation in cultured peripheral blood lymphocytes. The decrease in the tail moment and lipid peroxidation was significantly higher in combined supplementation of eugenol and anethole as compared to individual administration. The results of the present study suggests ameliorative role of eugenol and anethole against arsenic induced genotoxic and oxidative damage in cultured human peripheral blood lymphocytes.

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