Genotoxicity of Paragonimus heterotremus Infection in a Rat Model of Simultaneous Pulmonary and Hepatic Paragonimiasis

Parasites cause numerous health issues in humans, eventually leading to significant social and economic damage; however, the mechanisms of parasite-mediated pathogenesis are not well understood. Nevertheless, it is clearly evidenced that cancerogenic fluke-induced chronic inflammations and cancer are closely associated with oxidative stress. (1) Methods: The Paragonimus heterotremus infection’s genotoxic potential was assessed in a rat model of simultaneous pulmonary and hepatic paragonimiasis by the alkaline version of single-cell gel electrophoresis (comet assay). Statistical analysis of comet parameters was based on the non-parametric Mann–Whitney U test. (2) Results: A clear and statistically significant increase in DNA damage was detected in the helminth-exposed group versus the control rats and the tissue areas adjacent to the parasite capsule versus remote ones; however, differences in DNA damage patterns between different tissues were not statistically significant. Infection resulted in up to 40% cells with DNA damage and an increased genetic damage index. (3) Conclusions: The data obtained contribute to understanding the pathogenesis mechanisms of paragonimiasis, suggesting oxidative stress as the most likely reason for DNA breaks; these findings allow us to consider P. heterotremus as a potentially cancerogenic species, and they are important for the monitoring and treatment of paragonimiasis.

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Nuclear Damage in Peripheral Erythrocytes of Cyprinus Carpio Exposed to Binary Mixture of Pesticides

Journal of Zoo Biology ◽

10.33687/zoobiol.002.01.1506 ◽

2019 ◽

Vol 2 (1) ◽

pp. 39-47

Author(s):

Faiza Ambreen ◽

Muhammad Javed

Keyword(s):

Dna Damage ◽

Cyprinus Carpio ◽

Peripheral Blood ◽

Damage Index ◽

Tail Length ◽

Time Dependent ◽

Lethal Concentration ◽

Static System ◽

Genetic Damage ◽

Long Duration

The present study was undertaken to examine the DNA damage in peripheral blood erythrocytes of Cyprinus carpio under the binary exposure of bifenthrin and chlorpyrifos by using single cell gel electrophoresis (SCGE). Limited efforts have been made to study the genotoxic effect for long duration period. Therefore, the present investigation was aimed to assess the genotoxicity of pesticide mixture to the freshwater carp, Cyprinus carpio at sub-lethal concentration exposure (33% LC50). At first 96-hr LC50 value of pesticide, the mixture was determined for Cyprinus carpio in a static system and then sub-lethal concentration was calculated and fish was exposed to this sub-lethal concentration of the mixture in glass aquaria for 70 days (five fortnights) at constant laboratory conditions. Peripheral blood erythrocytes were taken on a fortnightly basis for the time-dependent DNA damage assessment in-terms of percentage of damaged cells, genetic damage index and a cumulative tail length of comets. Concentration-dependent increase in the percentage of DNA damaged cells were observed up to a 4th fortnight, followed by a slight decrease in the 5th fortnight. Similarly, statistically significant time-dependent DNA damage was observed in terms of percentage of damaged cells, genetic damage index and a cumulative tail length of comets in treated fish (at 33% of LC50) as compared to control groups. The results supported the use of SCGE for evaluating the toxicity of pollutants which may be used as part of environmental monitoring programs.

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Assessment of ecotoxicological effects of ciprofloxacin in Daphnia magna: life-history traits, biochemical and genotoxic effects

Water Science & Technology ◽

10.2166/wst.2018.255 ◽

2018 ◽

Vol 2017 (3) ◽

pp. 835-844 ◽

Cited By ~ 1

Author(s):

B. Nunes ◽

C. Leal ◽

S. Rodrigues ◽

S. C. Antunes

Keyword(s):

Oxidative Stress ◽

Life History ◽

Daphnia Magna ◽

Metabolic Response ◽

Damage Index ◽

Continuous Exposure ◽

Genetic Damage ◽

Genotoxic Effects ◽

Damage Scenarios ◽

Life History Parameters

Abstract Antibiotics (e.g. ciprofloxacin) have been detected in surface water and groundwater for several decades. In order to understand the potential impact of the continuous exposure of aquatic organisms to ciprofloxacin, a chronic assay was carried out with Daphnia magna. This approach allowed evaluation of the effects of ciprofloxacin on life-history and sub-individual parameters (antioxidant status and metabolic response: activities of catalase and glutathione S-transferases – GSTs; peroxidative damage; thiobarbituric acid reactive substances and genotoxic effects (genetic damage index, measured by the comet assay). Life-history parameters of D. magna showed no significant effects after ciprofloxacin exposure. Concerning oxidative stress and metabolism parameters, no significant alterations were reported for catalase and GSTs activities. However, a dual response was observed, with a significant decrease in lipid peroxidation levels at low ciprofloxacin concentrations (<0.013 mg/L), while a significant increase was verified at high ciprofloxacin concentrations (0.078 mg/L). The genotoxicity assay detected a significant increase in genetic damage index up to 0.013 mg/L of ciprofloxacin. The here-tested ciprofloxacin concentrations, which are ecologically relevant, did not cause significant impacts concerning the life-history parameters of D. magna; however, at the same levels of ciprofloxacin an oxidative stress and genotoxic damage scenarios were recorded.

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Dysregulation of X-Ray Repair Cross Complementing 4 Expression in the Eutopic Endometrium of Women with Endometriosis

Reproduction ◽

10.1530/rep-21-0436 ◽

2022 ◽

Author(s):

Kashmira Bane ◽

Junita Desouza ◽

Asma Rojewale ◽

Rajendra Katkam ◽

Gwendolyn Fernandes ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Critical Role ◽

Dna Lesions ◽

Dna Breaks ◽

Eutopic Endometrium ◽

Nhej Pathway ◽

X Ray ◽

Protein Levels ◽

Ishikawa Cells

Recent data suggest that the DNA damage response (DDR) is altered in the eutopic endometrium (EE) of women with endometriosis and this probably ensues in response to higher DNA damage encountered by the EE in endometriosis. DDR operates in a tissue-specific manner and involves different pathways depending on the type of DNA lesions. Among these pathways, the non-homologous end joining (NHEJ) pathway plays a critical role in the repair of double-stranded DNA breaks. The present study was undertaken to explore whether NHEJ is affected in the EE of women with endometriosis. Towards this, we focused on the X-Ray Repair Cross-Complementing 4 (XRCC4) protein, one of the core components of the NHEJ pathway. Endometrial XRCC4 protein levels in the mid-proliferative phase were found significantly (p<0.05) downregulated in women with endometriosis, compared to control women. Investigation of a microarray-based largest dataset in the GEO database (GSE51981) revealed a similar trend at the transcript level in the EE of women with endometriosis, compared to control women. Further in-vitro studies were undertaken to explore the effects of H2O2-induced oxidative stress on DNA damage, as assessed by γ-H2AFX and 8-hydroxy-2’-deoxyguanosine (8-OHdG) immunolocalization, and XRCC4 protein levels in endometrial stromal (ThESCs) and epithelial (Ishikawa) cells. A significant decrease in XRCC4 protein levels and significantly higher localization of γ-H2AFX and 8-OHdG were evident in ThESCs and Ishikawa cells experiencing oxidative stress. Overall, the study demonstrates that the endometrial XRCC4 expression is dysregulated in women with endometriosis and this could be due to higher oxidative stress in endometriosis.

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Association between genotoxic properties of inhalation anesthetics and oxidative stress biomarkers

Toxicology and Industrial Health ◽

10.1177/0748233720935696 ◽

2020 ◽

Vol 36 (6) ◽

pp. 454-466

Author(s):

Masoud Neghab ◽

Fatemeh Kargar-Shouroki ◽

Hossein Mozdarani ◽

Saeed Yousefinejad ◽

Hamzeh Alipour ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Operating Room ◽

Antioxidant Status ◽

Venous Blood ◽

Exposed Group ◽

Oxidative Stress Biomarkers ◽

Operating Room Personnel ◽

Cross Sectional ◽

Inhalation Anesthetics

Exposure to inhalation anesthetics (IAs) has been associated with DNA damage as reflected in the increased frequency of micronuclei (MN) and chromosomal aberrations (CAs). The present study was undertaken to ascertain whether there was any correlation between increased MN and CA and the extent of oxidative stress as well as the antioxidant status of a group of operating room personnel exposed to a mixture of IAs, including nitrous oxide, isoflurane, and sevoflurane. In this cross-sectional study, 60 operating room personnel (exposed group) in whom the frequencies of MN and CA had already been shown to be significantly higher than those of a referent group, as well as 60 unexposed nurses, were studied. Venous blood samples were taken from all participants, and malondialdehyde (MDA) levels as an index of oxidative stress (OS) and the activity of superoxide dismutase (SOD) and levels of total antioxidant capacity (TAC) as indices of antioxidant status were measured. The level of TAC (1.76 ± 0.59 mM vs. 2.13 ± 0.64 mM, p = 0.001) and the activity of SOD (11.22 ± 5.11 U/ml vs. 13.36 ± 4.12 U/ml, p = 0.01) were significantly lower, while the mean value of MDA was significantly higher (2.46 ± 0.66 µM vs. 2.19 ± 0.68 µM, p = 0.03) in the exposed group than in the nonexposed group. After adjusting for potential confounders, there were statistically significant associations between exposure to IAs, gender, SOD, and TAC with MN frequency and between exposure to IAs and SOD with numbers of CA. The findings of the present study indicated that exposure to IAs was associated with OS, and this, in turn, may be causally linked with DNA damage.

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Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

Cellular Physiology and Biochemistry ◽

10.1159/000443050 ◽

2016 ◽

Vol 38 (3) ◽

pp. 982-992 ◽

Cited By ~ 20

Author(s):

Abderrahim Nemmar ◽

Suhail Al-Salam ◽

Priya Yuvaraju ◽

Sumaya Beegam ◽

Javed Yasin ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Lung Function ◽

Respiratory System ◽

Lung Inflammation ◽

Experimental Studies ◽

Damage Index ◽

Water Pipe ◽

First Time ◽

And Oxidative Stress

Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS) adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months). Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the long-term effects of WPS on the respiratory system.

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Cooperation of the Cockayne Syndrome Group B Protein and Poly(ADP-Ribose) Polymerase 1 in the Response to Oxidative Stress

Molecular and Cellular Biology ◽

10.1128/mcb.25.17.7625-7636.2005 ◽

2005 ◽

Vol 25 (17) ◽

pp. 7625-7636 ◽

Cited By ~ 75

Author(s):

Tina Thorslund ◽

Cayetano von Kobbe ◽

Jeanine A. Harrigan ◽

Fred E. Indig ◽

Mette Christiansen ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Cellular Response ◽

Genetic Disorder ◽

Cockayne Syndrome ◽

Dna Lesions ◽

Dna Breaks ◽

Group B ◽

Parp 1

ABSTRACT Cockayne syndrome (CS) is a rare genetic disorder characterized as a segmental premature-aging syndrome. The CS group B (CSB) protein has previously been implicated in transcription-coupled repair, transcriptional elongation, and restoration of RNA synthesis after DNA damage. Recently, evidence for a role of CSB in base excision repair of oxidative DNA lesions has accumulated. In our search to understand the molecular function of CSB in this process, we identify a physical and functional interaction between CSB and poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is a nuclear enzyme that protects the integrity of the genome by responding to oxidative DNA damage and facilitating DNA repair. PARP-1 binds to single-strand DNA breaks which activate the catalytic ability of PARP-1 to add polymers of ADP-ribose to various proteins. We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. Furthermore, we find that CSB-deficient cell lines are hypersensitive to inhibition of PARP. Our results implicate CSB in the PARP-1 poly(ADP-ribosyl)ation response after oxidative stress and thus suggest a novel role of CSB in the cellular response to oxidative damage.

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Quantification of double stranded DNA breaks and telomere length as proxies for corneal damage and replicative stress in 64 human keratoconus corneas

10.1101/244871 ◽

2018 ◽

Author(s):

Robert PL Wisse ◽

Jonas JW Kuiper ◽

Timothy RDJ Radstake ◽

Jasper CA Broen

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Telomere Length ◽

Morphological Changes ◽

Corneal Transplant ◽

Dna Breaks ◽

Alu Elements ◽

Contact Lens Wear ◽

Replicative Stress ◽

Corneal Sample

AbstractPurposeThe pathogenesis of keratoconus (KC) is multifactorial and associated with oxidative stress and subsequent DNA damage. The aim of this study was to investigate differences in DNA damage and replicative stress in patients with KC, and in both healthy and diseased controls.MethodsSixty-four corneal buttons were obtained from 27 patients with KC after corneal transplant surgery, 21 patients with a decompensated graft (DG), and 16 healthy controls (HC). The amount of intact Alu elements per genome copy as measured by qPCR was used to quantify intact DNA. Telomere length was measured as a proxy for replicative stress. In addition, telomerase reverse transcriptase (hTERT) gene expression level was assessed.ResultsMean (±SD) DNA damage was similar between the KC (5.56 ±14.08), DG (3.16 ±8.22), and HC (3.51 ±6.66) groups (P=0.807). No associations were found between DNA damage and patient age (P=0.523), atopic constitution (P=0.240), or contact lens wear (P=0.393). Telomere length differed (P=0.034), most notably in the KC group, and hTERT was not detected in any corneal sample. Three cross-linked (CXL) KC corneas did not contain significant more DNA damage (2.6x, P = 0.750).ConclusionsBased on these findings, differences in actual corneal DNA damage in KC could not be identified, and the longer telomere length in KC did not support replicative stress as a major etiological factor in the pathogenesis of KC. Future longitudinal investigations on KC etiology should assess progressive early cases to better comprehend the cellular and molecular processes preceding the archetypical morphological changes.PrecisOxidative stress is allegedly linked with the development of keratoconus. Whether these stressors actually lead to persisting DNA damage and replicative stress is debated. DNA damage was comparable with control samples, and a shortened telomere length was not identified.

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GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/782123 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 10

Author(s):

Svetlana Kostyuk ◽

Tatiana Smirnova ◽

Larisa Kameneva ◽

Lev Porokhovnik ◽

Anatolij Speranskij ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Dna Damage ◽

Mesenchymal Stem Cells ◽

Dna Damage Response ◽

Extracellular Dna ◽

Dna Breaks ◽

Rt Pcr ◽

Double Strand Dna Breaks ◽

Damage Response

Background. Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA.Principal Findings. Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA) and results in both single- and double-strand DNA breaks (comet assay andγH2AX, foci). As a result in the cells significantly increases the expression of repair genes (BRCA1(RT-PCR), PCNA (FACS)) and antiapoptotic genes (BCL2(RT-PCR and FACS),BCL2A1,BCL2L1, BIRC3, andBIRC2(RT-PCR)). Under the action of GC-DNA the potential of mitochondria was increased. Here we show that GC-rich extracellular DNA stimulates adipocyte differentiation of human adipose-derived mesenchymal stem cells (haMSCs). Exposure to GC-DNA leads to an increase in the level of RNAPPARG2andLPL(RT-PCR), in the level of fatty acid binding protein FABP4 (FACS analysis) and in the level of fat (Oil Red O).Conclusions. GC-rich fragments in the pool of cfDNA can potentially induce oxidative stress and DNA damage response and affect the direction of mesenchymal stem cells differentiation in human adipose—derived mesenchymal stem cells. Such a response may be one of the causes of obesity or osteoporosis.

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Mesenchymal Stem Cells Early Response to Low-Dose Ionizing Radiation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.584497 ◽

2020 ◽

Vol 8 ◽

Author(s):

Marina Konkova ◽

Margarita Abramova ◽

Andrey Kalianov ◽

Elizaveta Ershova ◽

Olga Dolgikh ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Stem Cells ◽

Dna Damage ◽

Mesenchymal Stem Cells ◽

Ionizing Radiation ◽

Low Dose ◽

Early Response ◽

Dna Breaks ◽

Essential Components

IntroductionMesenchymal stem cells (MSCs) are applied as the therapeutic agents, e.g., in the tumor radiation therapy.Purpose of the StudyTo evaluate the human adipose MSC early response to low-dose ionizing radiation (LDIR).Materials and MethodsWe investigated different LDIR (3, 10, and 50 cGy) effects on reactive oxygen species production, DNA oxidation (marker 8-oxodG), and DNA breaks (marker ɣ H2AX) in the two lines of human adipose MSC. Using reverse transcriptase–polymerase chain reaction, fluorescence-activated cell sorting, and fluorescence microscopy, we determined expression of genes involved in the oxidative stress development (NOX4), antioxidative response (NRF2), antiapoptotic and proapoptotic response (BCL2, BCL2A1, BCL2L1, BIRC2, BIRC3, and BAX1), in the development of the nuclear DNA damage response (DDR) (BRCA1, BRCA2, ATM, and P53). Cell cycle changes were investigated by genes transcription changes (CCND1, CDKN2A, and CDKN1A) and using proliferation markers KI-67 and proliferating cell nuclear antigen (PCNA).ResultsFifteen to 120 min after exposure to LDIR in MSCs, transient oxidative stress and apoptosis of the most damaged cells against the background of the cell cycle arrest were induced. Simultaneously, DDR and an antiapoptotic response were found in other cells of the population. The 10-cGy dose causes the strongest and fastest DDR following cell nuclei DNA damage. The 3-cGy dose induces a less noticeable and prolonged response. The maximal low range dose, 50 cGy, causes a damaging effect on the MSCs.ConclusionTransient oxidative stress and the death of a small fraction of the damaged cells are essential components of the MSC population response to LDIR along with the development of DDR and antiapoptotic response. A scheme describing the early MSC response to LDIR is proposed.

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Bridging a Gap between Cr(VI)-Induced Oxidative Stress and Genotoxicity in Lettuce Organs after a Long-Term Exposure

International Journal of Agronomy ◽

10.1155/2018/5738014 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Cristina Monteiro ◽

Sara Sario ◽

Rafael Mendes ◽

Nuno Mariz-Ponte ◽

Sónia Silva ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Crop Production ◽

Antioxidant Activities ◽

Dependent Manner ◽

Dna Breaks ◽

Arable Soils ◽

Genotoxic Effects ◽

Organ Specific

Chromium (Cr) contamination in arable soils and irrigating water remains a priority, particularly due to the challenges posed to crop production and food safety. Long-term Cr(VI) effects remain less addressed than short-term ones, particularly regarding organ-specific genotoxic profiles. Here we used the crop Lactuca sativa growing in a protected horticultural system and irrigated for 21 days with Cr(VI) (up to 200 mg/L). Besides the oxidative stress, the genotoxicity was evaluated. Shoots and roots showed distinctive oxidative stress status and genotoxic effects, in a dose-dependent manner. While 50 mg/L stimulated antioxidant activities and no major genotoxic effects were found, plants exposed to ≥150 showed an increase of oxidative disorders, together with cytostatic and DNA damage effects, and some mitotic impairment. Leaves showed less oxidative signs at 50 mg/L, while at 150/200 mg/L the antioxidant battery was stimulated. In Cr treated plants, the highest dose increased the DNA damage, reinforcing the idea that DNA breaks were related to mitotic disorders in higher doses. In conclusion, long-term exposure data show a highly responsive root, with a quadratic response meaning higher defenses at lower Cr doses, and higher oxidative and DNA damage and cytostatic effect at a higher dose.

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