Serum 8-OHdG Levels Research Articles

The effect of oral and intraurethral trimetazidine use on urethral healing.

We aimed to study the effect of trimetazidine (TMZ) on urethral wound repair. A total of 52 male rats were used; 8 groups were formed: 1-week and 3-week control (C1, C3), sham (S1, S3), oral (OT1, OT3), and intraurethral TMZ (IUT1, IUT3) groups. Serum and urine total antioxidant capacity (TAC), total oxidant capacity (TOC), and 8-hydroxy-deoxy-guanosine (8-OHdG) were studied. Hematoxyline-Eosin was used for the histopathological study. In addition, tumor necrosis factor alpha (TNF- α), interleukin 1α, and β levels were compared across groups by an immunohistochemical method. There were significant differences between C3 and IUT3, OT3 and IUT3 with respect to serum TAC in 3-week groups (P=0.013; P =0.001). Serum TOC levels were significantly different between C3 and IUT3; S3 and OT3; and OT3 and IUT3 groups (P =0.024; P =0.019; P =0.000, respectively). Serum 8-OHdG levels were significantly different between C3 and OT3 groups (P=0.033). In the immunohistochemical examination, C1 and OT1; C1 and IUT1; and S1, S3, OT1, OT3, IUT1 groups were significantly different with respect to IL-1β staining (P=0.007; P =0.000; P=0.009), while there was a significant difference between C3 and S3 with respect to IL-1β (P =0.000). TMZ increased urinary total oxidant level; while increasing serum TAC levels in the long-term. It also reduced serum TAC levels in urethral use and caused an increase in serum TOC levels with minimal effects on DNA injury and repair. No effect was detected on IL1 α and TNF, but partially reduced the effect on IL-1 β levels.

Oxidative DNA damage and oxidized low density lipoprotein in Type II diabetes mellitus among patients with Helicobacter pylori infection.

BackgroundHelicobacter pylori (H. pylori) infection is reported to be associated with various extragastrointestinal conditions such as insulin resistance, diabetes mellitus and metabolic syndrome. H. pylori infection and type 2 diabetes mellitus (T2DM) are associated with oxidative stress, this cross-relation between H. pylori induced infection in T2DM and oxidative damage is still debated. Thus, the question arises whether an increase in the serum level of 8-OHdG and Ox-LDL will occurs in patients with T2DM infected H. pylori; this will be through determination and compare frequency of H. pylori infection in T2DM and non-diabetic patients.Methods100 patients presented with history of epigastric discomfort for more than 1 month; 50 patients with T2DM and 50 non-diabetics. Anti-H. pylori IgG using ELISA, fasting and postprandial glucose level, glycated hemoglobin (HbA1c) and body mass index (BMI) was calculated. Serum 8-OHdG and Ox-LDL was measured using ELISA for the 100 patients and 50 control subject.ResultsRates of H. pylori infection of T2DM and non-diabetic were 66 and 58 %, respectively, (p = 0.001). H. pylori IgG antibody was not correlated with HbA1c either in T2DM (p = 0.06) or non-diabetic (p = 0.25). Serum 8-OHdG level in T2DM with positive H. pylori infection showed a significant difference compared to non-diabetics with positive H. pylori infection (p = 0.001) and higher than that in T2DM with negative H. pylori. A correlation between 8-OHdG concentration and HbA1c in T2DM patients infected with H. pylori was observed (r = 0.39, p = 0.02). Serum Ox-LDL level in T2DM with positive H. pylori infection showed a significant difference compared to diabetics with both negative H. pylori infection and in non-diabetics with positive H. pylori infection (p = 0.001).ConclusionsIncreased levels of oxidative DNA damage (8-OHdG) and Ox-LDL suggest the mechanistic link between H. pylori infection combined with diabetes and increased generation of ROS and could play as an important image for high risk to atherosclerosis.

Correlating blood levels of 8-hydroxydeoxyguanosine to hOGG1 genotypes and the incidence of ischemic cardiomyopathy

We measured the serum levels of 8-hydroxydeoxyguanosine (8-OHdG) and investigated whether these levels correlate with incidence of ischemic cardiomyopathy (ICM), and whether these levels correlate with underlying oxidative stress in patients with ICM. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to assess the prevalence of the Ser/Cys polymorphism in the human 8-oxoguanine glycosylase (hOGG1) gene. We analyzed the samples from 246 ICM cases (the ICM group) and another 246 age- and sex-matched volunteers with normal coronary artery function (the control group). Levels of 8-OHdG in participants' blood samples were 6.7 ± 1.7 and 3.0 ± 0.8 in the ICM and control groups, respectively (p < 0.05). Although there were no differences in allele frequency (p = 0.140), significant differences were present in the genotype distributions (p = 0.002). The Cys/Cys genotype correlated strongly with the risk of developing ICM (odds ratio, 2.2; 95% confidence interval, 1.4–3.3). Treating the Ser/Ser and Ser/Cys genotypes as members of the same group increased the predicted ICM risk for patients carrying the Cys/Cys genotype (odds ratio, 1.9; 95% confidence interval, 1.2–2.9). The serum level of 8-OHdG in the ICM group was higher than that in the control group (p < 0.05) and significantly increased in those carrying the Cys/Cys genotype (8.7 ± 1.7 for the Cys/Cys group, and 4.5 ± 0.8 for the Ser/Ser+Ser/Cys group; p < 0.05). Patients carrying the Cys/Cys genotype had a significantly increased risk of developing ICM. Serum levels of 8-OHdG were significantly increased in patients with ICM.

Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease.

ABSTRACTBackground and aimsInsulin resistance and cytokine production are key mechanisms leading to fatty change in the liver and may produce nonalcoholic steatohepatitis (NASH). Oxidative stress may also contribute to clinical progression from simple fatty liver (FL) to NASH. A therapy for insulin resistance and antioxidant has been applied to treat NASH, yet these treatments are not fully established. In the present study, we have evaluated whether an antioxidant agent, glutathione, prevents the development of NASH from FL.Materials and methodsFive patients with FL and 10 with NASH were enrolled in the study. Three hundred milligrams per day of glutathione was given orally to patients with nonalcoholic fatty liver disease (NAFLD) every day, and an oxidative stress marker and biochemical tests were analyzed before treatment and 1 and 3 months after starting the treatment. We measured serum levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and gamma-glutamyltranspeptidase (GGT). Immunohistochemistry for glutathione was performed on formalin fixed liver specimens obtained from liver biopsies.ResultsBefore treatment, the NASH group had higher serum 8-OHdG and lower serum glutathione levels than the FL group. Immunohistochemistry revealed that a strong expression of glutathione was observed in zone 3 in both NASH and FL before treatment. Serum levels of alanine transaminase and 8-OHdG were significantly decreased after treatment in the NASH group. Gamma-glutamyltranspeptidase was decreased after treatment, although the decrease was statistically not significant.DiscussionThe present pilot study demonstrated that antioxidant therapy with glutathione may reduce the pathological oxidative stress in the liver in NASH, preventing the progression from NAFLD to NASH.How to cite this articleIrie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S. Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(1):13-18.

Chromosomal aberrations and oxidative DNA adduct 8-hydroxy-2-deoxyguanosine as biomarkers of radiotoxicity in radiation workers

BackgroundThere are evidences of association between occupational radiation exposure, cytogenetic alterations and the increase in cancer rates. It is known that the probability of carcinogenesis is greater in populations exposed to radiation, since ionizing radiation can raise the frequency of chromosomal aberration and spontaneous mutations. ObjectiveOur purpose was to assess the role of chromosomal aberrations and oxidative DNA adduct 8-hydroxy-2-deoxyguanosine (8-OHdG) as biomarkers of radiation injury in individuals occupationally exposed to ionizing radiation. Subjectsand Methods: Blood samples were collected from 60 radiation workers and 30 healthy volunteers age and sex matched as control group who had never worked in radiation-related jobs. Chromosomal aberrations in peripheral blood lymphocytes were assayed by conventional cytogenetic technique and serum levels of 8-OHdG was measured by enzyme linked immunossorbent assay (ELISA). ResultsThe incidence of all types of chromosomal aberrations was significantly higher in all exposed groups than in controls with the highest rate of chromosomal aberrations in the industrial radiographers. Serum 8-OHdG in all radiation workers was significantly higher than in control group. There was a significant higher values among industrial radiographers compared to diagnostic radiologists or radiotherapists. Significantly lower mean corpuscular volume (M.C.V) was found among radiation workers versus the controls reflecting erythrocyte microcytosis. ConclusionsScoring of chromosome aberrations such as breaks, fragments and dicentrics is a reliable method to detect previous exposure to ionizing radiation. This type of monitoring may be used as a biological dosimeter instead of physical dosimetry.8-OHdG is a useful oxidative DNA marker among radiation workers and those exposed to environmental carcinogens.

Serum 8-hydroxy-2-deoxyguanosine as a marker of DNA oxidative damage in horses with recurrent airway obstruction.

BackgroundIt has been reported that equine recurrent airway obstruction (RAO) is a state of oxidative stress. Oxidant-antioxidant imbalance is known to increase the conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA. 8-OHdG can easily be measured using ELISA tests in serum or urine samples. In this study, we analysed serum 8-OHdG levels in horses with recurrent airway obstruction and in healthy controls.ResultsThe study material consisted of seven healthy horses and seven horses with symptomatic RAO. All horses were exposed to moldy hay and straw for 48 h to induce clinical exacerbation of RAO. The serum 8-OHdG levels were determined using the ELISA Highly Sensitive 8-OHdG kit. The difference between the levels of 8-OHdG in healthy and RAO-affected horses was significant. The median level of 8-OHdG was 0.044 ng/ml in the healthy controls versus 0.498 ng/ml in RAO horses (P = 0.0021).ConclusionsThe results of the study strongly suggest that DNA damage coexists in the course of equine RAO. We therefore propose that future research should aim at the development of new drugs that target pro-inflammatory molecules, since DNA damage appears to be the result of chronic inflammation.

P2-13: The therapeutic effects of dietary krill oil (euphausia superba) supplementation on serum oxidative stress and DNA damages markers in cafeteria-diet-overfed rats

Background The prevalence of obesity has increased dramatically in recent decades, so have the risks of associated medical conditions, such as type 2 diabete and cardiovascular disease, raising serious concerns for public health. Obesity is encouraged by current obesogenic environmental conditions that promote the intake of high-energy-dense foods and increased portion sizes. Cafeteria animal models provide a useful tool to study the metabolic syndrome in humans. Several animal studies and clinical trials suggest that marine bioactive oils supply may have potential effects on obesity and its associated features. Thus, the aim of this study was to evaluate the effects of krill oil enrichment in cafeteria-diet-overfed rats and their capacity to respond to acute changes on some antioxidant/ oxidant markers. Methods Eighteen aging male Wistar rats were divided into three groups of six each and were exposed for the ensuing 8 weeks to one of the diets : control group (C) which was submitted to standard chow (330kcal/100g), containing 24% of proteins, 5% of lipids and 70% of carbohydrates. Cafeteria standard group (CS) exposed to cafeteria diet (420kcal/100 g) containing 30 g of standard chow and 30 g of sausage-dry cookies mixture, cheese, chips, chocolate, and peanuts in proportions of 2:2:2: 1:1:1. The last group received a cafeteria diet enriched in oral force-feeding krill oil 2% (KO-CS). Results Despite modest differences in body weight, cafeteria-fed animals underwent an exacerbated body fat accumulation and increased metabolic risk. The substitution of standard chow diet by the cafeteria diet induced several disturbances in term of metabolic response to the radical attack in key tissues involved in antioxidant defense as demonstrated by the increase of TBARS, 8-OHdG DNA damages marker and isoprostanes levels in cafeteria-diet-fed rats. The serum TBARS, 8-OHdG and isoprostanes levels were significantly lowered by 45% and 25% respectively in the in the KO-CS group compared to CS group. Serum uric acid and albumin contents were decreased respectively by 36% and 18% in the krill oil enriched CS group as compared to cafeteria group. Conclusions A short period of exposure to a cafeteria diet in is enough to disturb the metabolic response to the radical attack in key tissues involved in antioxidant defense. The important antioxidant activity of KO could probably be due to its bioactive compounds (n-3 PUFA, phenolic compounds, alpha-tocopherol, manganese). Thus, its incorporation in a dietetic program can be strategically effective for the prevention/management, indeed improvement of free radical attack in obese subjects, which will prevent the obesity complications.

Abstract 14124: A Marked Increase in Myocardial Oxidative Stress Associated With Sympathetic Hyperactivity is Related to Transient Myocardial Dysfunction in Patients With Takotsubo Cardiomyopathy

Introduction: Sympathetic hyperactivity is considered as one of the most likely pathogenic mechanism in takotsubo cardiomyopathy (TC). However, little is known about the relationship between sympathetic hyperactivity and myocardial oxidative stress (OS). Hypothesis: We hypothesized that cardiac sympathetic hyperactivity was associated with cardiac myocardial OS, and OS related to transient myocardial dysfunction in patients with TC compared with acute anteroseptal myocardial infarction (AMI). Methods: In 8 TC patients and 8 AMI patients (NYHA 3), ECG, echocardiography, cardiac catheterization and serial measurements of plasma catecholamines, urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of OS and plasma CPK were performed for two weeks from onset. Results: Blood sampling from coronary sinus (CS) and aorta (Ao) at 1st day showed that norepinephrine (NE) levels and 8-OHdG level in CS were significantly higher than those in Ao and peripheral blood, indicating that an increase in myocardial OS was associated with cardiac sympathetic hyperactivity. NE levels in peripheral blood were peaked out at 1st day and 2-times higher in TC than in AMI within a week, while the max CPK value in TC was significantly lower than that in AMI. Dual scintigraphy of 201Tl and 123I-meta-iodobenzylguanidine was performed at 7th day showed that cardiac sympathetic nervous injury was much larger than myocardial perfusion damage in all TC patients. U-8OHdG level (ng/mg Cr; normal range:&lt;10.0) in TC was elevated in parallel with the profile of plasma NE level (1st day: 65.6±24.5, 4th day: 19.1±8.3, 7th day: 16.4±9.1), while it was decreased to almost normal range after percutaneous coronary intervention for left anterior descending artery in AMI (1st day: 24.3±13.8, 4th day: 9.8±3.4, 7th day: 12.3±2.7). Interestingly, difference in serum 8-OHdG levels (CS vs Ao) in TC increased proportionally with wall motion score (WMS) as an index of LV dysfunction (R=0.93, p&lt;0.001), while difference in serum NA levels (CA vs Ao) in TC did not. U-8OHdG level in TC was positively correlated with WMS at each day (1st day, 7th day). Conclusions: These findings suggest that myocardial OS induced by cardiac sympathetic hyperactivity may play a critical role in transient LV dysfunction in TC.

Serum 8 Hydroxydeoxyguanosine and Cytotoxin Associated Gene A as Markers for Helicobacter pylori Infection.

Helicobacter pylori (H.pylori) is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomas and mucosa associated tissue lymphomas. Cytotoxin associated gene A (CagA) is one of the virulence factors of H.pylori. It is hypothesized that reactive oxygen species (ROS) play roles in H.pylori associated disease especially in development of gastric adenocarcinoma. Individuals infected with H.pylori bearing CagA produce more ROS than others. 8-hydroxydeoxyguanosine (8OHdG) is an in vitro marker of DNA damage and oxidative stress. The aim of this study was to investigate the relationship between 8OHdG level, H.pylori infection and CagA and alterations of serum 8OHdG level after H.pylori eradication. Patients admitted with dyspeptic complaints and upper gastrointestinal endoscopy were assessed. H.pylori was determined from histopathology of specimens. Serum 8OHdG levels of three groups (H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive) were compared. Patients with H.pylori infection received eradication therapy. Serum 8OHdG levels pretreatment and posttreatment were also compared. In total, 129 patients (M/F, 57/72) were enrolled in the study. Serum 8OHdG level of H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive groups were significantly different (5.77±1.35 ng/ml, 5.43±1.14 ng/ml and 7.57±1.25 ng/ml respectively, p=0.05). Furthermore, eradication therapy reduced serum 8OHdG level (6.10±1.54 ng/ml vs 5.55±1.23 ng/ml, p=0.05). Individuals infected with H.pylori bearing CagA strains have the highest serum 8OHdG level and eradication therapy decreases the serum 8OHdG level. To the best of our knowledge this is the first study that evaluated the effect of CagA virulence factor on serum 8OHdG level and the effect of eradication therapy on serum 8OHdG levels together. Eradication of CagA bearing H.pylori may prevent gastric adenocarcinoma by decreasing ROS. 8OHdG level may thus be a good marker for prevention from gastric adenocarcinoma.

Preoperative serum 8-hydroxydeoxyguanosine is associated with chemoresistance and is a powerful prognostic factor in endometrioid-type epithelial ovarian cancer.

BackgroundOxidative stress is a widely seen phenomenon in several carcinomas. Increasing evidence also suggests that it has a significant role in the development of epithelial ovarian carcinoma (EOC). 8-Hydroxydeoxyguanosine (8-OHdG) is one of the main indicators of oxidative stress and increased expression of 8-OHdG has previously been seen in EOC. DJ-1 is an oncoprotein connected to oxidative stress regulation, but its role in ovarian cancer is not well known. We investigated redox status in different histotypes of EOC by measuring serum 8-OHdG and DJ-1 concentrations and their associations with known prognostic factors.MethodsSerum samples from newly diagnosed EOC patients were collected in 1996–2009 and stored at the Department of Obstetrics and Gynecology, Oulu University Hospital. Serum 8-OHdG and DJ-1 levels were measured by using commercially available ELISA kits. Clinical data was gathered retrospectively from the patients` files. Results were analyzed by using SPSS software.ResultsIn total, 112 patient samples were analyzed (38 serous, 20 mucinous, 34 endometrioid and 20 clear-cell). High serum 8-OHdG levels were associated with poor overall survival (OS) (p = 0.019), poor disease-free survival (DFS) (p = 0.020), platinum resistance (p = 0.002), serous histology versus other (p = 0.033), stage III–IV versus I–II (p = 0.009) and suboptimal surgical outcome (p = 0.012). Regarding histotypes, in the endometrioid EOC group in particular, serum 8-OHdG levels were significantly associated with poor DFS (p = 0.005), suboptimal surgical outcome (p = 0.025), and platinum resistance (p = 0.007). The prognostic significance of 8-OHdG in patients with endometrioid cancer in terms of DFS was confirmed in Cox regression analysis. High DJ-1 levels were associated with high histological grade (p = 0.029) and nonsignificantly associated with serous histology vs. other histology (p = 0.089).ConclusionsAn elevated serum 8-OHdG level is a significant predictor of poor prognosis, especially in cases of the endometrioid subtype of ovarian carcinoma. High 8-OHdG levels are associated with all traditional factors of poor prognosis in ovarian cancer and they also predict earlier development of platinum resistance. These results could be valuable when deciding the primary treatment mode for EOC patients.

Association of restless legs syndrome with oxidative stress and inflammation in patients undergoing hemodialysis

BackgroundRestless legs syndrome (RLS) is a common comorbidity in patients undergoing hemodialysis, but clinical factors predictive of RLS risk and severity have not been identified. The aims of this multicenter cross-sectional study were to document RLS prevalence and severity in patients undergoing hemodialysis and to identify associated risk factors. MethodsOne-hundred and fifty-nine stable patients on maintenance hemodialysis were enrolled (113 men, 46 women; mean age: 68 ± 11 years; mean duration of dialysis: 54 ± 60 months). Diagnosis of RLS was based on the criteria proposed by the International Restless Legs Syndrome Study Group (IRLSSG), and RLS severity was assessed using the IRLSSG Severity Scale. Potential factors associated with RLS and IRLSSG Severity Scale score were assessed by univariate and multivariate regression analyses. ResultsRLS affected 22% of the study population. The RLS subgroup had a significantly longer duration of hemodialysis and higher cardiothoracic ratio compared to the non-RLS subgroup. The RLS subgroup also had significantly higher serum levels of high-sensitivity C-reactive protein, interleukin-6, ferritin, N-terminal pro-B-type natriuretic peptide, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and a significantly lower transferrin saturation level compared to the non-RLS subgroup, suggesting a chronic inflammatory state and associated oxidative stress in comorbid patients. Serum 8-OHdG level was an independent risk factor for high IRLSSG Severity Scale score. ConclusionThis study confirms the high prevalence of RLS among hemodialysis patients and identifies the oxidative stress marker serum 8-OHdG as a significant independent predictor of RLS severity. Further studies are needed to identify detailed risk factors and the pathophysiological role of oxidative stress in RLS.

Evaluation of Lipid Peroxidation and Oxidative DNA Damage in Patients With Periodontitis and Hyperlipidemia

The purpose of this study is to determine the serum levels of malondialdehyde (MDA), as a lipid peroxidation marker, and 8-hydroxydeoxyguanosine (8-OHdG), as an oxidative DNA damage marker, in patients with chronic periodontitis (CP) and hyperlipidemia. A total of 74 individuals were divided into four age- and sex-matched groups: 18 patients with hyperlipidemia and CP (HLp), 18 periodontally healthy patients with hyperlipidemia (HLh), 19 systemically healthy individuals with CP (Cp), and 19 systemically and periodontally healthy controls (Ch). Clinical periodontal parameters were measured, and serum lipids, MDA, and 8-OHdG levels were assessed in blood samples. 8-OHdG, MDA, probing depth, clinical attachment level, and percentage of sites bleeding on probing (BOP) were significantly higher in the HLp group than the Cp group. In the hyperlipidemic group, BOP was significantly correlated with total cholesterol, the ratio of total cholesterol to high-density lipoprotein cholesterol, and 8-OHdG levels. A significant correlation between 8-OHdG and MDA was also observed in the hyperlipidemia group. In this study, serum MDA and 8-OHdG were found to be highest in the HLp group. The increased levels of MDA and 8-OHdG in HLp patients may be a result of a harmful oxidative status in association with hyperlipidemia and periodontitis.

Urinary 8-hydroxy-2′-deoxyguanosine as a novel biomarker of inflammatory activity in patients with cardiac sarcoidosis

BackgroundInflammation and oxidative stress play a crucial role in the pathogenesis of cardiac sarcoidosis (SAR). We investigated whether urinary (U) 8-hydroxy-2′-deoxyguanosine (8-OHdG)—an oxidative DNA damage marker—was related to SAR inflammatory activity. MethodsU-8-OHdG levels were measured in 31 SAR patients, classified as active (n=17) or non-active (n=14) based on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT), 28 dilated cardiomyopathy (DCM) patients, and 30 controls. In active SAR patients, U-8-OHdG levels were reexamined and compared with 18F-FDG-PET/CT results at 6months after corticosteroid treatment to assess therapeutic response. ResultsImmunohistochemical examination of left ventricle (LV) autopsy samples from SAR patients revealed positive 8-OHdG staining in cardiomyocyte nuclei from LV sections showing 18F-FDG accumulation on PET/CT, while serum 8-OHdG levels were significantly higher in the coronary sinus than in the aortic root only in active SAR patients. U-8-OHdG levels in SAR patients were higher than those in controls, and significantly higher in active SAR patients than in non-active SAR and DCM patients. U-8-OHdG was a powerful predictor of active SAR in receiver operating characteristic curve analysis (AUC, 0.98; 95% CI, 0.94–1.02; optimal cutoff value, 13.1ng/mg creatinine), with a sensitivity of 88.2% and a specificity of 92.9%. U-8-OHdG levels in responders significantly decreased at 6months after corticosteroid treatment initiation, in proportion with the decrease in the focal cardiac uptake of 18F-FDG. ConclusionsU-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients.

Epigenetic Study of Parkinson's Disease in Experimental Animal Model

Epigenetic modifications are defined as mechanisms that are able to modify the expression levels of selected genes without necessarily altering their DNA sequence, as histone tail modifications. These modifications are likely to contribute to the onset and progression of complex human diseases including neurodegenerative ones. Oxidative stress also is thought to be a common underlying mechanism that leads to cellular dysfunction and demise in PD. This study was aimed to assess the epigenetic fingerprint in PD experimental model through HDAC, PARP and activities oxidative stress markers. Materials and methods: The study was carried out on five rat groups, control group, Parkinsonism group, sodium butyrate group, two parkinson’s disease groups co-treated and post treated with sodium butyrate. Parkinsonism was induced by ip injection of paraquat. Laboratory measurements included serum 8-OHdG, MDA level as biomarkers of oxidative stress. HDAC and PARP activities were measured as other epigenetic mechanisms. Results: PD group, PD co-treated and post treated with sodium butyrate showed significant increase in HDAC and PARP activities. Also, there was significant increase in serum 8-OHdG level and MDA level in both serum and tissue. Conclusion and recommendations: The increments in HDAC and PARP activities are either two of the pathogenic mechanisms of the disease or it affords PD patients neuroprotection and benefits. Also, sodium butyrate is one of best antioxidant and neuroprotective agents. We recommended for further studies in HDAC and sodium butyrate as inhibitor in neurodegerative diseases, other diseases and normal state.

Inhibitory Effect of Various Breads on DMH-Induced Aberrant Crypt Foci and Colorectal Tumours in Rats

Bread is rich in dietary fibre and many phytochemical compounds, which may influence chemoprevention of colon cancer. In the present study, we evaluated the effect of three kinds of bread on DMH-induced colorectal tumours in F344 rats. F344 rats were divided into four groups (Steinmetz Three-Grain bread, Steinmetz Country bread, White bread, and MF). All groups were injected with 1,2-dimethylhydrazine (DMH, 20 mg/kg body weight) once a week for 8 consecutive weeks from 5 weeks of age. To investigate the antioxidant effect of bread, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging rate of bread and the serum levels of 8-hydroxy-deoxyguanosine (8-OHdG) in rats were examined. The number of colorectal aberrant crypt foci (ACF) and the incidence of colorectal tumours were studied after 34 weeks of DMH treatment. The Steinmetz Three-Grain and Steinmetz Country bread groups had higher scavenging rates of the DPPH free radical and lower serum levels of 8-OHdG and incidence of ACF, adenomas, and adenocarcinomas of colon than the White bread and MF group. Steinmetz Three-Grain bread and Steinmetz Country bread have various ingredient combinations that may inhibit colorectal cancer progression.

Markers of macromolecular oxidative damage in maternal serum and risk of neural tube defects in offspring

Neural tube defects (NTDs) are among the most common and severe congenital malformations. To examine the association between markers of macromolecular oxidative damage and risk of NTDs, we measured levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), and 8-iso-prostaglandin F2α (8-iso-PGF2α) in maternal serum samples of 117 women with NTD-affected pregnancies and 121 women with healthy term newborns. We found higher levels of 8-OHdG and PC in the NTD group than in the control group; however, we did not observe a statistically significant difference in 8-iso-PGF2α levels between the NTD and the control groups. NTD risk increased with increasing quartiles of 8-OHdG [odds ratio (OR)=1.17; 95% confidence interval (CI) 0.39–3.51; OR=2.19; 95% CI, 0.68–7.01; OR=3.70; 95% CI, 1.30–10.51, for the second, third, and fourth quartile relative to the lowest quartile, respectively; P=0.009], and with increasing quartiles of PC (OR=2.26; 95% CI, 0.66–7.69; OR=3.86; 95% CI, 1.17–12.80; OR=5.98; 95% CI, 1.82–19.66, for the second, third, and fourth quartile relative to the lowest quartile, respectively; P=0.002]. Serum levels of 8-OHdG were higher in women who did not take folic acid supplements during the periconceptional period. These results suggest that oxidative stress is present in women carrying pregnancies affected by NTDs.

Investigation of the role of 8-OHdG and oxidative stress in papillary thyroid carcinoma.

The aim of this study was to determine levels of serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an indicator of oxidant-induced DNA damage and oxidant status in patients with papillary thyroid carcinoma before and after surgery. This study included 25 patients with papillary thyroid carcinoma and age-matched 27 healthy controls. Total antioxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LOOH), and 8-OHdG levels were measured. 8-OHdG levels were significantly higher in the preoperative papillary thyroid carcinoma (PTC) group compared with the healthy control group (p < 0.001) and were significantly lower after operation in patients with papillary thyroid carcinoma (p = 0.004). Oxidative stress index (OSI) levels were significantly higher in both preoperative and postoperative PTC patients compared with the healthy control group (p < 0.001 and p < 0.001, respectively). TOS levels were higher in the preoperative and postoperative PTC groups compared to the healthy control group (p < 0.001 and p < 0.001, respectively). TAS levels was lower in the preoperative PTC groups compared to the healthy control group (p = 0.011). Serum LOOH levels were higher in both preoperative and postoperative PTC groups compared to the healthy control group (p < 0.001 and p < 0.001, respectively). Correlation analysis yielded that serum 8-OHdG levels were positively correlated with OSİ and LOOH levels in patients with PTC before surgery (r = 0.668, p < 0.001; r = 0.446, p = 0.025, respectively) and had a negative correlation with TAS levels (r = -0.616, p = 0.001). We have shown severe oxidative DNA damage and impaired antioxidant status in papillary thyroid carcinoma.

Efficacy of different doses of atorvastatin treatment on serum levels of 8-hydroxy-guanin (8-OHdG) and cardiac function in patients with ischemic cardiomyopathy.

Objective: To compare the efficacy of 40 mg and l0 mg atorvastatin on serum levels of 8-Hydroxy-Guanin (8-OHdG) and the cardiac function in patients with ischemic cardiomyopathy (ICM).Methods:One hundred twenty three hospitalized ICM patients and 120 healthy controls were included in this study. All subjects were randomly divided into two groups: 10 mg/d atorvastatin group (n=62) and 40 mg/d atorvastatin group (n=61). Serum levels of C-reactive protein (CRP), creatine kinase, glutamic-pyruvic transaminase, lipids and B-type natriuretic peptide (BNP) were tested in all subjects both at the initial phase and the terminal phase of this study. Adverse drug reaction events were recorded in this study. Echocardiographic method was applied to compare the cardiac function before and after treatment in the double blind study. Serum 8-OHdG levels were tested by enzyme-linked immunosorbent assay (ELISA) before and after treatment, and the results in atorvastatin treatment groups were compared with the healthy controls.Results:Serum 8-OHdG levels in ICM patients were significantly higher than that in normal control groups (p<0.05). There was significant difference of Serum 8-OHdG levels in 40 mg/d atorvastatin group (p<0.05), but was no significant difference in 10 mg/d atorvastatin group before and after the treatment. The 8-OHdG level in 40 mg/d atorvastatin group was significantly lower than that in 10 mg/d atorvastatin group before the treatment as well as after the treatment (p<0.05). The systolic and diastolic function improved significantly in 40 mg/d atorvastatin group before and after treatment, as well as in comparison with 10 mg/d atorvastatin group (p<0.05).Conclusion:Serum 8-OHdG possibly plays an important role in the pathogenesis of ICM. Atorvastatin is safe and effective in ICM treatment; furthermore atorvastatin which also has independent lipid lowering effect, is significantly better in the dose of 40 mg/day.

A Novel Preservation Solution Prolonged Cold Storage in Mouse Cardiac Grafts.

Background: We developed a novel non-potassium preservation solution contains L-cysteine, glycine, ascorbic acid/ascorbic acid-2-phosphate magnesium to prolonged mouse cardiac grafts cold storage. Methods: B6 mice underwent heterotopic heart transplantation and the animals were derived into 3 groups: recipients with non-preserved grafts (control group), recipients with grafts preserved in HTK solution for 24 and 48 hours (HTK-group), and recipients with grafts preserved in the new solution, called Solution II for 24 and 48 hours (S-II group). Recipient serum and grafts were harvest for assay. Results: In both 24hr- and 48hr-preservation series (24h- and 48h-series), time for restoration of heartbeat after reperfusion in S-II group was significantly shorter than in HTK group (HTK-24h: 306.2±39.6sec, S-II-24h: 110.5±20.3sec, p<0.01; HTK-48h: 1537.5±454.7sec, S-II-48h: 640±286sec, p<0.01). In 48h-series, Release of serum LDH, CK in S-II-group was significantly lower to compare with HTK group. The graft survival of HTK-48h group is 0 day (n=9), but S-II group is 9d, 17d, >100d×2. Graft ATP level of S-II-48h was significantly higher than HTK-48h. In both 24 and 48h-series, S-II significantly inhibited graft apoptosis. Moreover, immunohistochemistry staining revealed that the CD68-positive macrophage infiltration in S-II group was significantly lower compared with HTK group. In 24h-series, graft 8-OHdG positive cells (%) were significantly lower in S-II compared with HTK. Consistent with histologic findings, serum 8-OHdG levels were significantly inhibited in S-II group. Furthermore, the mRNA expression of the IL-6, HO-1, iNOS, CD11b in S-II-48h group, were significantly lower, wherever Nrf2, NF-κB, Arg-1, HIF-1α, TGF-β were significantly higher than HTK-48h group (p<0.01). Conclusion: Hence our data indicated that the novel preservation solution impairs graft macrophage infiltration, inhibits inflammatory cytokines and myocardial apoptosis which results in attenuating mouse cardiac grafts cold ischemia-reperfusion injury and prolonging cold storage.

Combined Treatment of Tacrolimus and Everolimus Increases Target Organ Injury Via Increasing P-Glycoprotein and Cytochrome P450.

It is not clear the influence of combined treatment of tacrolimus (TAC) and everolimus (EVR). In this study, we investigated; first, whether combined treatment of EVR and TAC affects organ dysfunction and oxidative stress; second, whether these combined treatment affect each drug level at the blood and target organ tissues and third, the mechanisms of drug-drug interaction by assessing P-glycoprotein and cytochrome P450.Rat was orally administrated with TAC (6 mg/kg/day) and EVR (1 or 2 mg/kg/day) for 4 weeks. The effect of EVR on TAC-induced organ injury was also compared with that of EVR and TAC treatment alone. Oxidative stress was measured with 8-hydroxy-2'-deoxyguanosin (8-OHdG) in serum and 24 hour urine. To confirm the drug interaction between and EVR or TAC, concentration of each drug was evaluated in the whole blood and tissue (kidney, pancreas and liver) using LC/MS/MS. The mechanism of drug interaction was evaluated by the expression of P-glycoprotein and cytochrome P450 in target organ tissues using immunoblot analysis. TAC or EVR treatment alone did not caused overt renal, pancreatic islet, and liver injury, but addition of EVR significantly increased the TAC-induced injury, as demonstrated by aggravated nephrotoxicity, pancreatic islet and liver dysfunction. In blood and target organs e.g. liver, kidney and pancreas, surprising higher TAC or EVR level were detected in combined group compared with single treated groups. And there was good correlation between two drugs in blood and target organs. The serum and urinary 8-OHdG level were significantly increased in the TAC and EVR combined treated group compared with the TAC or EVR alone group, and were well correlated with drug levels in the blood and tissues. TAC or EVR alone treated groups showed higher expression of P-glycoprotein than control, and combined treatment was further increased its expression compared to the TAC or EVR alone treatment groups. Consistently, cytochrome P450 also showed much higher level in combined group compared to the single treated groups. We conclude that addition of EVR aggravates TAC-induced organ injury and pharmacologic drug-drug interaction. The reason for drug interaction between two drugs is related to the mutual competitive interactions targeting P-glycoprotein and cytochrome P450.