ABSTRACT
Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.
Subject(s)
Arsenic , Environmental Exposure , Oxidative Stress , Adult , Female , Humans , Male , Middle Aged , 8-Hydroxy-2'-Deoxyguanosine , Arsenic/toxicity , Biomarkers/urine , China , Cross-Sectional Studies , DNA Damage , East Asian People , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Lipid Peroxidation/drug effects , Longitudinal Studies , Oxidative Stress/drug effectsABSTRACT
BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been linked to adverse birth outcomes that have been reported to be induced by oxidative stress, but few epidemiological studies to date have evaluated associations between urinary PAH metabolites and oxidative stress biomarkers in pregnancy and identified critical periods for these outcomes and PAH exposures in pregnancy. METHODS: A cohort of pregnant women was recruited early in pregnancy from antenatal clinics at the University of California Los Angeles during 2016-2019. We collected urine samples up to three times during pregnancy in a total of 159 women enrolled in the cohort. A total of 7 PAH metabolites and 2 oxidative stress biomarkers [malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)] were measured in all available urine samples. Using multiple linear regression models, we estimated the percentage change (%) and 95% confidence interval (CI) in 8-OHdG and MDA measured at each sample collection time per doubling of PAH metabolite concentrations. Furthermore, we used linear mixed models with a random intercept for participant to estimate the associations between PAH metabolite and oxidative stress biomarker concentrations across multiple time points in pregnancy. RESULTS: Most PAH metabolites were positively associated with both urinary oxidative stress biomarkers, MDA and 8-OHdG, with stronger associations in early and late pregnancy. A doubling of each urinary PAH metabolite concentration increased MDA concentrations by 5.8-41.1% and 8-OHdG concentrations by 13.8-49.7%. Linear mixed model results were consistent with those from linear regression models for each gestational sampling period. CONCLUSION: Urinary PAH metabolites are associated with increases in oxidative stress biomarkers during pregnancy, especially in early and late pregnancy.
Subject(s)
Biomarkers , Oxidative Stress , Polycyclic Aromatic Hydrocarbons , Humans , Female , Polycyclic Aromatic Hydrocarbons/urine , Los Angeles , Pregnancy , Adult , Biomarkers/urine , Young Adult , Environmental Pollutants/urine , 8-Hydroxy-2'-Deoxyguanosine/urine , Cohort Studies , Maternal Exposure/adverse effects , Malondialdehyde/urineABSTRACT
BACKGROUND: DNA is an important target for oxidative attack and its modification may increase the risk of mutagenesis. The aim of this study was to evaluate and compare salivary levels of the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in patients with oral cancer (OC) compared to the control group by a comprehensive search of the available literature. METHODS: The present systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/X3YMR. Four electronic databases were used to identify studies for this systematic review: PubMed, Scopus, ScienceDirect, and Web of Science from January 15, 2005, to April 15, 2021. The Joanna Briggs Institute (JBI) tool was used to assess article quality. RESULTS: Of the 166 articles identified, 130 articles were excluded on the basis of title and abstract screening (duplicates, reviews, etc.). Thirty-six articles were evaluated at full text and 7 articles met the inclusion criteria. Of these, only 5 studies had compatible data for quantitative analysis. An increase in salivary 8-OHdG levels was found in patients with OC compared to healthy subjects, but without statistical significance. 8-OHdG: SMD = 2,72 (95%CI= -0.25-5.70); *p = 0.07. CONCLUSIONS: This systematic review and meta-analysis suggests a clear trend of increased 8-OHdG levels in saliva of OC patients compared to the control group. However, further studies are required to clarify and understand the altered levels of this oxidative stress marker.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , Mouth Neoplasms , Oxidative Stress , Saliva , Humans , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Mouth Neoplasms/metabolism , Saliva/metabolism , Saliva/chemistry , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysisABSTRACT
Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy.
Subject(s)
DNA Damage , Iodine Radioisotopes , Oxidative Stress , Thyroid Cancer, Papillary , Thyroid Neoplasms , Thyroidectomy , Humans , Iodine Radioisotopes/therapeutic use , Iodine Radioisotopes/adverse effects , Thyroid Neoplasms/blood , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/pathology , Thyroid Neoplasms/genetics , Female , Male , Adult , Middle Aged , Thyroid Cancer, Papillary/blood , Thyroid Cancer, Papillary/radiotherapy , Oxidative Stress/drug effects , Micronucleus Tests , Carcinoma, Papillary/blood , Carcinoma, Papillary/pathology , Carcinoma, Papillary/radiotherapy , Carcinoma/radiotherapy , Carcinoma/blood , Carcinoma/genetics , Lymphocytes/radiation effects , Lymphocytes/drug effects , 8-Hydroxy-2'-Deoxyguanosine/blood , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Case-Control Studies , Genomic InstabilityABSTRACT
OBJECTIVE: The aim of the present study was the association between the relationship between Dietary Quality Index-International (DQI-I) and Healthy Eating Index (HEI) and the urinary levels of F2alpha-isoprostane (F2a-IP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was investigated as indicators of oxidative stress. RESULTS: Based on HEI (low, moderate, and good), the diet quality of both groups was classified as moderate. In all participants, HEI (ß=-0.29; P = 0.04) and DQI-I (ß=-0.46; P = 0.005) were inversely associated with 8-OHdG. Furthermore, a negative correlation was found between HEI (mean ß=-3.53; P = 0.04) and DQI-I (mean ß=-5.53; P = 0.004) with F2a-IP. The quality of the footballers' diet was higher than that of the control group. Following a high-quality diet, which is rich in antioxidants, is likely to effectively reduce oxidative stress.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , Biomarkers , Oxidative Stress , Humans , Male , Biomarkers/urine , 8-Hydroxy-2'-Deoxyguanosine/urine , Adult , Young Adult , Diet , Soccer/physiology , Diet, Healthy , F2-Isoprostanes/urine , Case-Control StudiesABSTRACT
BACKGROUND: Salivary oxidative stress has been extensively studied with attempts to correlate changes in the oxidative stress markers with local and systemic factors, including smoking. The objective of this study was to evaluate the influence of two forms of smoking, cigarettes and waterpipe smoking (WPS), on selected oxidative stress biomarkers in saliva. METHODS: Three groups of participants were enrolled into the study, controls (never smokers), cigarette smokers and WPS. Participants were clinically free from periodontitis and systemic conditions known to affect the saliva constituents. Unstimulated whole saliva samples were collected according to a standard protocol and concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (TAC), and cortisol. The one-way ANOVA test was used to compare the levels of each oxidative stress biomarker between the three study groups and the hierarchical linear regression analysis was used to test the levels of salivary cortisol for prediction of other oxidative stress biomarkers. Significance levels were set at 95% confidence intervals and probability values ≤0.05. RESULTS: 8-OHdG was highest in WPS group (mean±SE 11,030.35±1829.16 pg/mL) while MDA and cortisol levels were highest in the cigarette smokers group (mean±SE 3.33±0.52 µM and 3.99±0.48 ng/mL, respectively) and MPO was highest in the control group (mean±SE 7.760±1.55 ng/mL). WPS group showed the highest TAC (mean±SE 0.3±0.03 mM). However, none of the tested makers reached a statistically significant difference. CONCLUSIONS: Despite subtle changes in some biomarkers, the salivary oxidative stress does not appear to be significantly influenced by smoking habits in periodontitis-free smokers.
Subject(s)
Biomarkers , Oxidative Stress , Saliva , Humans , Oxidative Stress/physiology , Saliva/chemistry , Saliva/metabolism , Biomarkers/analysis , Biomarkers/metabolism , Cross-Sectional Studies , Male , Female , Adult , Periodontitis/metabolism , Malondialdehyde/metabolism , Malondialdehyde/analysis , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Peroxidase/metabolism , Peroxidase/analysis , Smoking/metabolism , Smoking/adverse effects , Water Pipe Smoking/adverse effects , Middle Aged , Hydrocortisone/metabolism , Hydrocortisone/analysisSubject(s)
8-Hydroxy-2'-Deoxyguanosine , Cheilitis , Humans , Cheilitis/pathology , Cheilitis/metabolism , ImmunohistochemistryABSTRACT
Low-dose 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been used to cope with skin photoaging, and is thought to involve DNA damage repair responses. However, it is still unknown how low-dose ALA-PDT regulates DNA damage repair to curb skin photoaging. We established a photoaging model using human dermal fibroblasts (HDFs) and rat skin. RNA-sequencing (RNA-seq) analysis was conducted to identify differentially expressed genes (DEGs) in HDFs before and after low-dose ALA-PDT treatment, followed by bioinformatics analysis. Senescence-associated ß-galactosidase (SA-ß-gal) staining was employed to assess skin aging-related manifestations and Western blotting to evaluate the expression of associated proteins. A comet assay was used to detect cellular DNA damage, while immunofluorescence to examine the expression of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in cells and skin tissues. In both in vivo and in vitro models, low-dose ALA-PDT alleviated the manifestations of ultraviolet B (UVB)-induced skin photoaging. Low-dose ALA-PDT significantly reduced DNA damage in photoaged HDFs. Furthermore, low-dose ALA-PDT accelerated the clearance of the photoproduct 8-oxo-dG in photoaged HDFs and superficial dermis of photoaged rat skin. RNA-seq analysis suggested that low-dose ALA-PDT upregulated the expression of key genes in the base excision repair (BER) pathway. Further functional validation showed that inhibition on BER expression by using UPF1069 significantly suppressed SA-ß-gal activity, G2/M phase ratio, expression of aging-associated proteins P16, P21, P53, and MUTYH proteins, as well as clearance of the photoproduct 8-oxo-dG in photoaged HDFs. Low-dose ALA-PDT exerts anti-photoaging effects by activating the BER signalling pathway.
Subject(s)
Aminolevulinic Acid , DNA Damage , DNA Repair , Fibroblasts , Photochemotherapy , Signal Transduction , Skin Aging , Ultraviolet Rays , Aminolevulinic Acid/pharmacology , DNA Repair/drug effects , Animals , Ultraviolet Rays/adverse effects , Humans , Skin Aging/drug effects , Skin Aging/radiation effects , Signal Transduction/drug effects , Photochemotherapy/methods , Rats , Fibroblasts/metabolism , Fibroblasts/drug effects , Fibroblasts/radiation effects , DNA Damage/drug effects , Skin/drug effects , Skin/metabolism , Skin/radiation effects , Skin/pathology , Male , Photosensitizing Agents/pharmacology , 8-Hydroxy-2'-Deoxyguanosine/metabolismABSTRACT
Atherosclerotic plaque instability increases the risk of stroke. As such, determining the nature of an instability atherosclerotic plaque may speed up qualification for carotid endarterectomy (CEA), thus reducing the risk of acute vascular events. The aim of the study was to determine the diagnostic value of oxidized LDL cholesterol (ox-LDL), matrix metalloproteinase 9 (MMP-9) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum as a prognostic markers of instability atherosclerotic plaques. Serum was collected from 67 patients who underwent CEA in accordance with the qualification criteria. The levels of ox-LDL, MMP-9 and 8-OHdG were assessed by ELISA. The predictive value of the markers was determined based on an ROC curve, and the cut-off points with the highest sensitivity and specificity were determined. Patients with unstable atherosclerotic plaque had significantly higher serum ox-LDL, MMP-9 and 8-OHdG values. It was found that in patients before CEA, ox-LDL >31.4 ng/mL was associated with an 82.5% probability of unstable atherosclerotic plaque, MMP-9 >113.1 ng/mL with 78.6%, and 8-OHdG >2.15 ng/mL with 64.7%. Multivariate regression analysis found ox-LDL to be an independent factor associated with plaque instability. Patients with unstable plaques tend to have higher serum levels of ox-LDL, MMP-9 and 8-OHdG compared to those with stable plaques. The optimal cut-off point for ox-LDL (AUC 0.86, p <0.0001) was 31.14 ng/mL, with 91.18% sensitivity and 78.79% specificity. The high sensitivity and specificity of ox-LDL suggests that it can be used as an independent marker of plaque instability.
Subject(s)
Biomarkers , Endarterectomy, Carotid , Lipoproteins, LDL , Matrix Metalloproteinase 9 , Plaque, Atherosclerotic , Humans , Lipoproteins, LDL/blood , Plaque, Atherosclerotic/surgery , Plaque, Atherosclerotic/blood , Plaque, Atherosclerotic/pathology , Male , Female , Biomarkers/blood , Prognosis , Matrix Metalloproteinase 9/blood , Aged , Middle Aged , ROC Curve , 8-Hydroxy-2'-Deoxyguanosine/bloodABSTRACT
Purpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNFα], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1ß], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNFα, COX-2, IL-1ß, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants.
Subject(s)
Apoptosis , Benzhydryl Compounds , DNA Damage , Endocrine Disruptors , Gallic Acid , Ovary , Oxidative Stress , Phenols , Animals , Female , Gallic Acid/pharmacology , Benzhydryl Compounds/toxicity , Ovary/drug effects , Ovary/metabolism , Oxidative Stress/drug effects , Endocrine Disruptors/toxicity , Rats , DNA Damage/drug effects , Apoptosis/drug effects , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Interleukin-1beta/metabolism , Interleukin-1beta/genetics , Protective Agents/pharmacology , Luteinizing Hormone/blood , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/metabolism , Rats, Sprague-Dawley , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Progesterone , Humans , Antioxidants/pharmacology , Malondialdehyde/metabolism , Superoxide Dismutase/metabolismABSTRACT
The genome is continuously exposed to a variety of harmful factors that result in a significant amount of DNA damage. This article examines the influence of a multi-damage site containing oxidized imino-allantoin (OXIa) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (OXOdG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[A1OXIa2A3OXOG4A5]*d[T5C4T3C2T1] structure was obtained at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the condensed phase, with the energies obtained at the M06-2X/6-31++G** level. The non-equilibrated and equilibrated solvent-solute interactions were also considered. Theoretical studies reveal that the radical cation prefers to settle on the OXOG moiety, irrespective of the presence of OXIa in a ds-oligo. The lowest vertical and adiabatic ionization potential values were found for the OXOG:::C base pair (5.94 and 5.52 [eV], respectively). Conversely, the highest vertical and adiabatic electron affinity was assigned for OXIaC as follows: 3.15 and 3.49 [eV]. The charge transfers were analyzed according to Marcus' theory. The highest value of charge transfer rate constant for hole and excess electron migration was found for the process towards the OXOGC moiety. Surprisingly, the values obtained for the driving force and activation energy of electro-transfer towards OXIa2C4 located this process in the Marcus inverted region, which is thermodynamically unfavorable. Therefore, the presence of OXIa can slow down the recognition and removal processes of other DNA lesions. However, with regard to anticancer therapy (radio/chemo), the presence of OXIa in the structure of clustered DNA damage can result in improved cancer treatment outcomes.
Subject(s)
Allantoin , DNA , Oxidation-Reduction , Allantoin/chemistry , DNA/chemistry , 8-Hydroxy-2'-Deoxyguanosine/chemistry , DNA Damage , Thermodynamics , Models, MolecularABSTRACT
Photochemical reactions in cell DNA are induced in various organisms by solar UV radiation and may lead to a series of biological responses to DNA damage, including apoptosis, mutagenesis, and carcinogenesis. The chemical nature and the amount of DNA lesions depend on the wavelength of UV radiation. UV type B (UVB, 290-320 nm) causes two main lesions, cyclobutane pyrimidine dimers (CPDs) and, with a lower yield, pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). Their formation is a result of direct UVB photon absorption by DNA bases. UV type A (UVA, 320-400 nm) induces only cyclobutane dimers, which most likely arise via triplet-triplet energy transfer (TTET) from cell chromophores to DNA thymine bases. UVA is much more effective than UVB in inducing sensitized oxidative DNA lesions, such as single-strand breaks and oxidized bases. Of the latter, 8-oxo-dihydroguanine (8-oxodG) is the most frequent, being produced in several oxidation processes. Many recent studies reported novel, more detailed information about the molecular mechanisms of the photochemical reactions that underlie the formation of various DNA lesions. The information is mostly summarized and analyzed in the review. Special attention is paid to the oxidation reactions that are initiated by reactive oxygen species (ROS) and radicals generated by potential endogenous photosensitizers, such as pterins, riboflavin, protoporphyrin IX, NADH, and melanin. The review discusses the role that specific DNA photoproducts play in genotoxic processes induced in living systems by UV radiation of various wavelengths, including human skin carcinogenesis.
Subject(s)
DNA Damage , Pyrimidine Dimers , Ultraviolet Rays , Ultraviolet Rays/adverse effects , Humans , DNA Damage/radiation effects , Pyrimidine Dimers/metabolism , Pyrimidine Dimers/genetics , Pyrimidine Dimers/radiation effects , Reactive Oxygen Species/metabolism , DNA/radiation effects , DNA/metabolism , DNA/genetics , Animals , Apoptosis/radiation effects , Oxidation-Reduction/radiation effects , 8-Hydroxy-2'-Deoxyguanosine/metabolismABSTRACT
Water is a major requirement for our bodies, and alkaline water has induced an antioxidant response in a model of natural aging. A series of recent reports have shown that aging is related to reduced water intake. Hydrogen-rich water has been suggested to exert a general antioxidant effect in relation to both improving lifestyle and preventing a series of diseases. Here, we wanted to investigate the effect of the daily intake of hydrogen-rich alkaline water (HAW) in counteracting the redox imbalance induced in a model of H2O2-treated mice. Mice were treated with H2O2 for two weeks and either left untreated or supplied with HAW. The results show that HAW induced a reduction in the ROS plasmatic levels that was consistent with the increase in the circulating glutathione. At the same time, the reduction in plasmatic 8-hydroxy-2'-deoxyguanosine was associated with reduced DNA damage in the whole body. Further analysis of the spleen and bone marrow cells showed a reduced ROS content consistent with a significantly reduced mitochondrial membrane potential and superoxide accumulation and an increase in spontaneous proliferation. This study provides evidence for a clear preventive and curative effect of HAW in a condition of systemic toxic condition and redox imbalance.
Subject(s)
Hydrogen Peroxide , Hydrogen , Oxidation-Reduction , Reactive Oxygen Species , Water , Animals , Mice , Hydrogen Peroxide/metabolism , Hydrogen/pharmacology , Oxidation-Reduction/drug effects , Reactive Oxygen Species/metabolism , Water/chemistry , Oxidative Stress/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , DNA Damage/drug effects , Male , Membrane Potential, Mitochondrial/drug effects , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Glutathione/metabolism , Dietary SupplementsABSTRACT
Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2'-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls (p = 0.03), particularly in ET (p = 0.04) and PMF (p = 0.01). MPL W515L-positive MPNs had higher TAC than controls (p = 0.002) and triple-negative MPNs (p = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects (p = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; p = 0.05), i.e., ET (OR = 2.36; p = 0.03) and PMF (OR = 2.11; p = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; p = 0.62) or sAML (OR = 1.89; p = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , Antioxidants , Myeloproliferative Disorders , Humans , Male , Female , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Middle Aged , Aged , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/metabolism , Myeloproliferative Disorders/pathology , Antioxidants/metabolism , Adult , Oxidative Stress , Aged, 80 and over , Blast Crisis/metabolism , Blast Crisis/genetics , Blast Crisis/pathology , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Primary Myelofibrosis/genetics , Primary Myelofibrosis/metabolism , Primary Myelofibrosis/pathologyABSTRACT
Objectives: To examine changes in tear oxidative stress levels and tear film functions in patients with blepharoptosis and dermatochalasis following conjunctiva-Müller muscle resection (CMMR) and blepharoplasty surgeries. Materials and Methods: This prospective study included 32 healthy controls and 62 patients with blepharoptosis or dermatochalasis. CMMR surgery was performed in 20 eyes and upper blepharoplasty was performed in 42 eyes. Tear oxidative stress markers (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 4-hydroxy-2-nonenal [4-HNE]) were quantified by enzyme-linked immunosorbent assay and tear film functions were evaluated preoperatively and at 1 and 6 months postoperatively. The same assessments were performed in the control group at the same time points. Results: Preoperative tear 8-OHdG and 4-HNE levels were lower in healthy controls (52.8±13.5 ng/mL and 27.8±6.4 ng/mL, respectively) compared to patients with dermatochalasis (86.1±37.2 ng/mL and 29.8±11.1 ng/mL, respectively) and blepharoptosis (90.4±39.3 ng/mL and 43.1±4.2 ng/mL, respectively) (p<0.001). 8-OHdG levels were increased at 1 month after CMMR, while both markers were decreased 1 month postoperatively in the blepharoplasty group (p=0.034). Schirmer 1 and OSDI scores did not change throughout the visits in both patient groups, but a temporary decrease in tear break-up time (TBUT) was observed after CMMR (p=0.017). Conclusion: Dermatochalasis and blepharoptosis were associated with higher tear oxidative stress levels. CMMR surgery caused a temporary decrease in TBUT scores and an increase in oxidative stress in the first postoperative month.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , Blepharoplasty , Blepharoptosis , Conjunctiva , Oculomotor Muscles , Oxidative Stress , Tears , Humans , Oxidative Stress/physiology , Blepharoptosis/surgery , Blepharoptosis/metabolism , Female , Male , Prospective Studies , Tears/metabolism , Blepharoplasty/methods , Middle Aged , Conjunctiva/metabolism , Conjunctiva/surgery , Oculomotor Muscles/surgery , Oculomotor Muscles/metabolism , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Adult , Biomarkers/metabolism , Enzyme-Linked Immunosorbent Assay , Aged , Aldehydes/metabolismABSTRACT
Formamidopyrimidine (Fapyâ¢dG) is a major lesion arising from oxidation of dG that is produced from a common chemical precursor of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). In human cells, replication of single-stranded shuttle vectors containing Fapyâ¢dG is more mutagenic than 8-OxodGuo. Here, we present the first data regarding promoter dependent RNA polymerase II bypass of Fapyâ¢dG. 8-OxodGuo bypass was examined side-by-side. Experiments were carried out using double-stranded shuttle vectors in HeLa cell nuclear lysates and in HEK 293T cells. The lesions do not significantly block transcriptional bypass efficiency. Less than 2% adenosine incorporation occurred in cells when the lesions were base paired with dC. Inhibiting base excision repair in HEK 293T cells significantly increased adenosine incorporation, particularly from Fapyâ¢dG:dC bypass which yielded â¼25% adenosine incorporation. No effect was detected upon transcriptional bypass of either lesion in nucleotide excision repair deficient cells. Transcriptional mutagenesis was significantly higher when shuttle vectors containing dA opposite one of the lesions were employed. For Fapyâ¢dG:dA bypass, adenosine incorporation was greater than 85%; whereas 8-OxodGuo:dA yielded >20% point mutations. The combination of more frequent replication mistakes and greater error-prone Pol II bypass suggest that Fapyâ¢dG is more mutagenic than 8-OxodGuo.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , DNA Damage , Deoxyguanosine , Promoter Regions, Genetic , RNA Polymerase II , Humans , RNA Polymerase II/metabolism , RNA Polymerase II/genetics , HEK293 Cells , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , HeLa Cells , DNA Repair , Transcription, Genetic , Pyrimidines , Pyrimidine Dimers/metabolism , Pyrimidine Dimers/geneticsSubject(s)
8-Hydroxy-2'-Deoxyguanosine , Cheilitis , Humans , Cheilitis/pathology , Cross-Sectional Studies , Immunohistochemistry , CausalityABSTRACT
8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) base is the predominant form of commonly observed DNA oxidative damage. DNA impairment profoundly impacts gene expression and serves as a pivotal factor in stimulating neurodegenerative disorders, cancer, and aging. Therefore, precise quantification of 8-oxoG has clinical significance in the investigation of DNA damage detection methodologies. However, at present, the existing approaches for 8-oxoG detection pose challenges in terms of convenience, expediency, affordability, and heightened sensitivity. We employed the sandwich enzyme-linked immunosorbent assay (ELISA) technique, a highly efficient and swift colorimetric method, to detect variations in 8-oxo-dG content in MCF-7 cell samples stimulated with different concentrations of hydrogen peroxide (H2O2). We determined the concentration of H2O2 that induced oxidative damage in MCF-7 cells by detecting its IC50 value in MCF-7 cells. Subsequently, we treated MCF-7 cells with 0, 0.25, and 0.75 mM H2O2 for 12 h and extracted 8-oxo-dG from the cells. Finally, the samples were subjected to ELISA. Following a series of steps, including plate spreading, washing, incubation, color development, termination of the reaction, and data collection, we successfully detected changes in the 8-oxo-dG content in MCF-7 cells induced by H2O2. Through such endeavors, we aim to establish a method to evaluate the degree of DNA oxidative damage within cell samples and, in doing so, advance the development of more expedient and convenient approaches for DNA damage detection. This endeavor is poised to make a meaningful contribution to the exploration of associative analyses between DNA oxidative damage and various domains, including clinical research on diseases and the detection of toxic substances.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , DNA Damage , Enzyme-Linked Immunosorbent Assay , Hydrogen Peroxide , Oxidative Stress , Humans , DNA Damage/drug effects , MCF-7 Cells , Enzyme-Linked Immunosorbent Assay/methods , Hydrogen Peroxide/pharmacology , Oxidative Stress/drug effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/analysisABSTRACT
BACKGROUND: The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism. METHODS: ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells. CONCLUSION: PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.
Subject(s)
Apoptosis , Cell Survival , Oxidative Stress , Peroxiredoxins , Reactive Oxygen Species , Retinal Pigment Epithelium , Ultraviolet Rays , Humans , Retinal Pigment Epithelium/radiation effects , Retinal Pigment Epithelium/metabolism , Peroxiredoxins/metabolism , Ultraviolet Rays/adverse effects , Reactive Oxygen Species/metabolism , MAP Kinase Signaling System/physiology , Cell Line , Blotting, Western , Cells, Cultured , 8-Hydroxy-2'-Deoxyguanosine/metabolism , Signal TransductionABSTRACT
The genome-the source of life and platform of evolution-is continuously exposed to harmful factors, both extra- and intra-cellular. Their activity causes different types of DNA damage, with approximately 80 different types of lesions having been identified so far. In this paper, the influence of a clustered DNA damage site containing imidazolone (Iz) or oxazolone (Oz) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (OXOdG) on the charge transfer through the double helix as well as their electronic properties were investigated. To this end, the structures of oligo-Iz, d[A1Iz2A3OXOG4A5]*d[T5C4T3C2T1], and oligo-Oz, d[A1Oz2A3OXOG4A5]*d[T5C4T3C2T1], were optimized at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the aqueous phase using the ONIOM methodology; all the discussed energies were obtained at the M06-2X/6-31++G** level of theory. The non-equilibrated and equilibrated solvent-solute interactions were taken into consideration. The following results were found: (A) In all the discussed cases, OXOdG showed a higher predisposition to radical cation formation, and B) the excess electron migration toward Iz and Oz was preferred. However, in the case of oligo-Oz, the electron transfer from Oz2 to complementary C4 was noted during vertical to adiabatic anion relaxation, while for oligo-Iz, it was settled exclusively on the Iz2 moiety. The above was reflected in the charge transfer rate constant, vertical/adiabatic ionization potential, and electron affinity energy values, as well as the charge and spin distribution. It can be postulated that imidazolone moiety formation within the CDL ds-oligo structure and its conversion to oxazolone can significantly influence the charge migration process, depending on the C2 carbon hybridization sp2 or sp3. The above can confuse the single DNA damage recognition and removal processes, cause an increase in mutagenesis, and harm the effectiveness of anticancer therapy.