8-hydroxy-2--deoxyguanosine and Obesity

Elevated LDL-C, lipoprotein(a) [Lp(a)], and inflammation are associated with greater risk for atherosclerotic cardiovascular events. Consumption of individual nut types decreases these risk factors but knowledge about the effect of mixed nuts on Lp(a) is limited. The objective of this study was to determine the effects of consuming 42.5 g/day of mixed nuts on LDL-C, Lp(a), and inflammatory markers in individuals with overweight or obesity.. Consumption of mixed nuts had no evidence of an effect on LDL-C or Lp(a) throughout the intervention. Notably, mixed nut consumption lowered body fat percentage without significant changes in body weight or BMI. Future studies with larger sample sizes investigating the changing trends of CRP, 8-oxodG, and TAC are warranted.. NCT03375866.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adiponectin; Adult; Cardiometabolic Risk Factors; Cholesterol, LDL; Humans; Inflammation; Lipoprotein(a); Nuts; Obesity; Overweight; Risk Factors

Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage.. Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles.. We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05).. Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antigens, Differentiation; Antioxidants; Breakfast; Cross-Over Studies; Deoxyguanosine; Dimethylpolysiloxanes; DNA Damage; DNA Glycosylases; Female; Humans; Male; Middle Aged; Obesity; Olive Oil; Oxidative Stress; Plant Oils; Postprandial Period; Rapeseed Oil; RNA, Messenger; Sunflower Oil; Tumor Suppressor Protein p53

To examine the relationship between maternal smoking during pregnancy and the body composition of offspring.. Grade 4 elementary school children (n=1366; boys/girls, 724/642; 9-10 years old) were enrolled in this study. All parents answered a lifestyle questionnaire, and children underwent passive smoking tests. Urinary cotinine measurement and lifestyle screening test parameters (that is, body weight, body length, body mass index (BMI), obesity index (OI), blood tests for liver function and lipid profile and questions regarding maternal smoking and lifestyle) were evaluated in terms of their relationship with maternal smoking. In addition, urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was measured in 80 randomly selected children to assess its relationship with oxidative stress.. Both BMI and OI were significantly higher in children whose mothers smoked during pregnancy than in those whose mothers never smoked (BMI: 17.2±2.7 vs 16.9±2.5 kg m(-2), P=0.016; OI: 2.7±14.3% vs 0.4±14.0%, P=0.003). The degree of elevation was positively correlated with the duration of maternal smoking. The increases in BMI and OI resulted from increased body weight and reduced height. The confounding factors-'breakfast with family', 'watching television at dinner', 'eating and drinking before sleep', 'watching television for >2 h', 'sleep duration <8 h' and 'playing sports'-were statistically significant. BMI and OI were significantly high in children whose mothers smoked during pregnancy in these six confounders. On the other hand, urinary 8-OHdG concentration was negatively correlated with BMI in children who had >1.3 ng ml(-1) urinary cotinine, suggesting that it may be related to basal metabolism due to oxidative stress.. Maternal smoking is a risk factor for higher BMI and OI in 9- to 10-year-old children whose mothers smoke during pregnancy and may be independent of other confounding factors.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Body Composition; Body Mass Index; Child; Cross-Sectional Studies; Deoxyguanosine; Female; Humans; Japan; Male; Obesity; Oxidative Stress; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Retrospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; Tobacco Smoke Pollution

Zonulin is observed in animal models to regulate intestinal permeability and influenced by dietary intake, gut microbiota, and inflammation. We conducted a secondary analysis of a randomized controlled crossover trial (NCT03582306) in individuals with a BMI greater than 30 kg/m. Participants were provided with frozen GLV during the first or last four weeks (immediate or delayed intervention) of the twelve-week trial. Biological and anthropometric measures were taken at the beginning and at each four-week interval. A subset of 20 participants was selected for this secondary analysis of the intestinal permeability and inflammation-related biomarkers: serum and fecal zonulin; serum lipopolysaccharide binding protein (LBP), Alpha-1-acid glycoprotein 1 (ORM-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and C-reactive protein; 8-hydroxy-2'-deoxyguanosine (8OHdG) and plasma Vitamin K1 as a marker of protocol adherence. Nutrient and food group intake from two-24-h dietary recalls collected at each time point were assessed. Fecal microbiota was measured by 16 s rRNA PCR sequencing. Changes in biological markers, dietary factors, and microbial taxa were assessed with Wilcoxon Sign Ranks Tests. Exploratory analyses of the relationship between changes in outcome variables were conducted with Spearman correlations.. No changes in serum and fecal zonulin and serum LBP were observed. Plasma Vitamin K (p = 0.005) increased, while plasma 8OHdG (p = 0.023) decreased during the intervention compared to the control. The only dietary factors that changed significantly were increases during intervention in Vitamin K and Dark GLV (p < 0.001 for both) compared to control. Fecal microbiota did not change significantly across all times points; however, change in serum zonulin was associated with change in Proteobacteria (ρ = - 0.867, p = 0.001) in females and Bifidobacterium (ρ = - 0.838, p = 0.009) and Bacteroidaceae (ρ = 0.871, p = 0.005) in men.. A high GLV dietary intervention increased serum zonulin levels and had no effect on fecal zonulin. Lack of concordance between several inflammation-associated biomarkers and zonulin corroborate recent reports of limited utility of zonulin in obese adults free of lower gastrointestinal disease. Trial Registration information: https://clinicaltrials.gov/ct2/show/NCT03582306 (NCT03582306) registered on 07/11/2018.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cross-Over Studies; Feces; Female; Haptoglobins; Humans; Inflammation; Obesity; Protein Precursors; Randomized Controlled Trials as Topic; Vegetables; Vitamin K

Emerging evidence from rodent studies suggests that high-fat-diet (HFD)-induced obesity is characterized by increased oxidative damage in sperm and testis. However, interventions using micronutrient supplementation to mitigate oxidative damage in obesity have not been extensively studied. This study aimed to investigate the effect of an antioxidant-based micronutrient supplement (added folate, vitamin B. Rats (3-weeks-old, 12/group) were weaned onto control (C) or HFD (H) or these diets with micronutrient supplement (CS; HS); sperm and testis were harvested at 30.5 weeks. To assess oxidative stress and antioxidant capacity in testis, levels of malondialdehyde (MDA), glutathione (GSH), folate and susceptibility index (SI) of pro-oxidative damage, mRNA expression of Nrf2, NFκB-p65, IL-6, IL-10 and TNF-α, in addition to superoxide-dismutase (SOD), catalase and glutathione-peroxidase (GPx) activities were measured. 8-hydroxy-2-deoxyguanosine (8-OHdG) were assessed in both sperm and testis.. HFD-fed rats had significantly increased 8-OHdG content in sperm and testis, increased testicular SI, decreased testicular weight, SOD and GPx activity compared to control. Strikingly, supplementation of HFD appeared to significantly reduce 8-OHdG in sperm and testis (22% and 24.3%, respectively), reduce testicular SI and MDA content (28% and 40%, respectively), increase testicular weight (24%), SOD and GPX activity (30% and 70%, respectively) and GSH content (19%). Moreover, supplementation had significant impact to increase testicular folate content regardless of diet. Furthermore, an overall effect of supplementation to increase testicular mRNA expression of Nrf2 was observed across groups. Interestingly, testicular SI was positively correlated with sperm and testicular 8-OHdG and MDA content, suggesting a critical role of testicular antioxidant activity to combat oxidative damage in sperm and testis.. Our findings suggest that antioxidant-based micronutrient supplement has the potential to interrupt HFD-induced sperm and testicular oxidative damage by improving testicular antioxidant capacity.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Diet, High-Fat; Folic Acid; Glutathione; Male; Micronutrients; NF-E2-Related Factor 2; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; RNA, Messenger; Semen; Spermatozoa; Superoxide Dismutase; Testis

Ultra-processed food is one of the main contributors to energy supply and consumption in food systems worldwide, and evidence of their detrimental health outcomes in humans is emerging. This study aimed to assess ultra-processed food intake and its association with urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in 139 healthy adolescents in Karaj City in Iran. Usual dietary intake was measured using a 168-item validated FFQ. The daily intake of ultra-processed food consumption was determined through the classification of NOVA, and general linear models were used to compare the urinary levels of 8-OHdG/creatinine (ng/mg creatinine) within tertiles of ultra-processed food intake. Adolescents in the higher tertile of ultra-processed food consumption had a significantly higher mean level of urinary 8-OHdG/creatinine in comparison with the lower tertiles in the crude model (Pfor trend: 0·003) and after adjustment for confounding variables, including total energy intake, sex, age, BMI for age Z-score, obesity and physical activity (Pfor trend: 0·004). This association was still significant after adjusting for dietary intake of whole grains, nuts, legumes, the ratio of MUFA:SFA (g/d) and Mediterranean dietary score (Pfor trend: 0·002). More studies are needed to explore the determinants of ultra-processed food supply, demand, consumption and health effects; such studies should be applied to develop evidence-informed policies and regulatory mechanisms to improve children's and adolescents' food environment policymaking and legislation with special attention to ultra-processed food.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Biomarkers; Body Mass Index; Diet; DNA Damage; Edible Grain; Energy Intake; Female; Food Handling; Humans; Iran; Male; Obesity; Sex Factors; Young Adult

The progression of nonalcoholic fatty liver disease (NAFLD) into severe histological forms (steatohepatitis - NASH) is paralleled by the occurrence of complex molecular processes. Mitochondrial dysfunction is a hallmark feature of advanced disease. Mitochondrially encoded cytochrome B (cytochrome b, MT-CYB), a member of the oxidative phosphorylation system, is a key component of the respirasome supercomplex. Here, we hypothesized that NAFLD severity is associated with liver tissue cytochrome b mutations and damaged mitochondrial DNA (mtDNA).. We included 252 liver specimens of NAFLD patients - in whom histological disease ranged from mild to severe - which were linked to clinical and biochemical information. Tissue molecular explorations included MT-CYB sequencing and analysis of differential mtDNA damage. Profiling of circulating Krebs cycle metabolites and global liver transcriptome was performed in a subsample of patients. Tissue levels of 4-hydroxynonenal - a product of lipid peroxidation and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative damage - were measured.. Compared to simple steatosis, NASH is associated with a higher level of MT-CYB variance, 12.1 vs. 15.6 substitutions per 10. NASH is associated with genetic alterations of the liver cellular respirasome, including high cytochrome b variation and mtDNA damage, which may result in broad cellular effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aldehydes; Amino Acids, Branched-Chain; Cytochromes b; Disease Progression; DNA Damage; DNA, Mitochondrial; Glutamic Acid; Glutarates; Humans; Lipid Peroxidation; Liver; Middle Aged; Mutation; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Phosphorylation; Oxidative Stress; Severity of Illness Index; Transcriptome

Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB-indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; DNA; Female; Gastric Bypass; Humans; Male; Middle Aged; Obesity; Oxidative Stress; RNA

Adiponectin plays a role in asthma and obesity, but its effects and mechanism in obesity-related asthma remain elusive. This study aimed to evaluate the effects of adiponectin on airway inflammation and oxidative stress and to determine its mechanism in obesity-related asthma. Male C57BL6/J mice fed with a high-fat diet to induce obesity were sensitized and challenged with ovalbumin to induce asthma, and treated with adiponectin (1 mg/kg) and AMP-activated protein kinase (AMPK) inhibitor compound C (20 mg/kg) twice before the first ovalbumin challenge. We found exogenous adiponectin significantly reduced airway resistance, inflammatory infiltration in lung tissue, and cell counts in bronchoalveolar lavage fluid. Adiponectin inhibited great levels of eotaxin, myeloperoxidase, tumor necrosis factor-α, 8‑hydroxy‑2'‑deoxyguanosine, and nitric oxide in obesity-related asthma mice. Moreover, we found increased nuclear factor kappa B p65, inducible nitric oxide synthase and B-cell lymphoma 2 protein expression were down-regulated with adiponectin administration. Additionally, adiponectin elevated the lower levels of pAMPK and AMPK activity in lung tissue. These protective effects of adiponectin were reversed after treatment with the AMPK inhibitor compound C. Thus, we conclude that adiponectin alleviates exacerbation of airway inflammation and oxidative stress in a murine model of obesity-related asthma partly through AMPK signaling pathway.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adiponectin; AMP-Activated Protein Kinases; Animals; Antioxidants; Asthma; Chemokine CCL11; Deoxyguanosine; Immunoglobulin E; Inflammation; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Obesity; Oxidative Stress; Random Allocation

Objective To compare the level of oxidative deoxyribonucleic acid (DNA) damage (genotoxicity) between the offspring of mothers with and without diabetes diagnosed during pregnancy and its association with maternal body mass index (BMI). Methods We measured 8-hydroxy-deoxyguanosine (8-OH-dG), a marker of DNA oxidative damage, in venous umbilical cord plasma from newborns of mothers with (n=34) and without (n=56) diabetes diagnoses obtained during pregnancy. Two markers of oxidative stress - namely, nitric oxide degradation products (NOx) and total glutathione (GSH) - were quantified in both mothers and newborns. The effects of BMI, glycated hemoglobin (HbA1c), age and delivery mode were also analyzed. Results Newborns of mothers with diabetes during pregnancy exhibited higher levels of 8-OH-dG than those of mothers without diabetes (P<0.001). The other markers of oxidative stress were also higher in both mothers with diabetes and their newborns, with the exception of NOx in the mothers. The association of diabetes with 8-OH-dG was independent of other analyzed factors. Conclusion The offspring of mothers with diabetes during pregnancy are born with increased genotoxicity than the offspring of mothers without diabetes. BMI and HbA1c display an independent association with 8-OH-dG, particularly in the offspring of mothers not diagnosed with diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Deoxyguanosine; Diabetes, Gestational; DNA Damage; Female; Humans; Infant, Newborn; Obesity; Oxidative Stress; Pregnancy; Young Adult

Oxidative stress has been linked to cancer development in previous studies. However, the association between pre-diagnostic oxidatively generated DNA/RNA damage levels and incident cancer has rarely been investigated. Urinary oxidized guanine/guanosine (OxGua) concentrations, including 8-hydroxy-2'-deoxyguanosine, were assessed in 8,793 older adults in a population-based German cohort. 1,540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were diagnosed during over 14 years of follow-up. Associations of OxGua levels with cancer outcomes were not observed in the total population in multi-variable adjusted Cox regression models. However, in subgroup analyses, colorectal cancer incidence increased by 8%, 9% and 8% with one standard deviation increase in OxGua levels among current non-smokers, female and non-obese participants, respectively. Additionally, among non-smokers, overall and prostate cancer incidences statistically significantly increased by 5% and 13% per 1 standard deviation increase in OxGua levels, respectively. In contrast, OxGua levels were inversely associated with the risk of prostate cancer among current smokers. However, none of the subgroup analyses had p-values below a threshold for statistical significance after correction for multiple testing. Thus, results need to be validated in further studies. There might be a pattern that oxidatively generated DNA/RNA damage is a weak cancer risk factor in the absence of other strong risk factors, such as smoking, obesity and male sex.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Breast Neoplasms; Colorectal Neoplasms; DNA Damage; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Obesity; Oxidative Stress; Prostatic Neoplasms; Risk Factors; Sex Factors; Smoking

Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.. A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.. SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).. Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cholesterol, HDL; Deoxyguanosine; Female; Genetic Association Studies; Genetic Pleiotropy; Humans; Lipase; Lipids; Male; Middle Aged; Models, Biological; Obesity; Polymorphism, Single Nucleotide; Sex Characteristics; Triglycerides

Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play an important role in the onset and progression of renal cell carcinoma (RCC). However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2 isoenzymes, has not been studied in RCC yet. Two coding single nucleotide polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925) causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697) causing asparagine to aspartate substitution (*N142D), and have been associated with several neurodegenerative diseases and cancers. Functional relevance of yet another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we aimed to assess the effect of specific GSTO1 and GSTO2 gene variants, independently and in interaction with established risk factors (smoking, obesity and hypertension) on the risk for the most aggressive RCC subtype, the clear cell RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were determined by ELISA. As a result, combined effect of all three variant genotypes exhibited almost 3-fold risk of RCC development. Additionally, this association was confirmed at the haplotype level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype], suggesting a potential role of those variants in propensity to RCC. Regarding the gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are at higher ccRCC risk. Association in terms of oxidative DNA damage was found for GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO polymorphisms may influence ccRCC risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Carcinoma, Renal Cell; Case-Control Studies; Deoxyguanosine; Female; Genetic Predisposition to Disease; Glutathione Transferase; Haplotypes; Humans; Hypertension; Kidney Neoplasms; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Risk Factors

8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been recently shown to exert anti-inflammatory effects through inhibition of Rac1. Inflammation in adipose tissue is a hallmark of obesity-induced insulin resistance, but the therapeutic potential of 8-OHdG in treatment of metabolic diseases has not been fully elucidated. The aim of this study was to examine the effect of exogenously administered 8-OHdG on adipose tissue and whole body metabolism. In cultured adipocytes, 8-OHdG inhibited adipogenesis and reversed TNFα-induced insulin resistance. In high-fat diet (HFD)-induced obese mice, 8-OHdG administration blunted the rise in body weight and fat mass. The decrease in adipose tissue mass by 8-OHdG was due to reduced adipocyte hypertrophy through induction of adipose triglyceride lipase and inhibition of fatty acid synthase expression. 8-OHdG also inhibited the infiltration of macrophages, resulting in amelioration of adipose tissue inflammation and adipokine dysregulation. Moreover, 8-OHdG administration ameliorated adipocyte as well as systemic insulin sensitivity. Both in vivo and in vitro results showed that 8-OHdG induces AMPK activation and reduces JNK activation in adipocytes. In conclusion, our results show that orally administered 8-OHdG protects against HFD-induced metabolic disorders by regulating adipocyte metabolism.

Topics: 3T3-L1 Cells; 8-Hydroxy-2'-Deoxyguanosine; Adipocytes; Animals; Cell Differentiation; Cells, Cultured; Deoxyguanosine; Diet, High-Fat; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Tumor Necrosis Factor-alpha

Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adiponectin; Adult; Age Factors; Biomarkers; Body Mass Index; Case-Control Studies; Deoxyguanosine; DNA; Female; Gene Expression; Gestational Age; Humans; Leptin; Malondialdehyde; Neural Networks, Computer; Obesity; Oxidative Stress; Pregnancy; Pregnancy Trimester, Third; Protein Carbonylation; Resistin; Severity of Illness Index

Association of exposure to polycyclic aromatic hydrocarbons (PAHs) with increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation has been reported in occupational population and children. However, studies on the association between them in general population are limited. A total of 1864 eligible subjects from the baseline Wuhan participants of the Wuhan-Zhuhai Cohort Study (n = 3053) were included in this study, after excluding individuals with certain disease and missing data on urinary monohydroxy PAHs (OH-PAHs) and 8-OHdG levels. Urinary monohydroxy PAHs and 8-OHdG levels were measured by gas chromatography-mass spectrometry and high performance liquid chromatography-electrochemical detection, respectively. Association of urinary OH-PAHs with urinary 8-OHdG was analyzed by multiple linear regression analysis. We found a dose-dependent relationship between urinary PAHs metabolites and urinary 8-OHdG (p < 0.05 for all). Furthermore, more evidence for the association of total concentrations of urinary OH-PAHs with 8-OHdG levels were observed in individuals with normal body mass index or central obesity (p < 0.01 for all). There was a dose-dependent relationship between urinary OH-PAHs levels and urinary 8-OHdG levels among a general Chinese population. Exposure to background PAHs may have a greater influence on urinary 8-OHdG levels in individuals with central obesity.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Asian People; Biomarkers; Chromatography, High Pressure Liquid; Cohort Studies; Deoxyguanosine; Dose-Response Relationship, Drug; Environmental Monitoring; Environmental Pollutants; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Obesity; Polycyclic Aromatic Hydrocarbons

Recent studies have shown adverse effects on the periodontium from the increased production of reactive oxygen species (ROS) in obesity. The purpose of this study was to investigate the effects of obesity on 8-hydroxy-deoxyguanosine (8-OHdG) levels in the bodily fluids of patients with and without periodontal disease and to evaluate changes after initial periodontal treatment.. Forty-five obese individuals and 45 normal-weight individuals were included in this study. Obese and normal-weight groups were classified into three sub-groups: chronic periodontitis (CP), gingivitis (G) and periodontally healthy controls (CTRL). Gingival crevicular fluid (GCF), plasma, saliva samples and clinical measurements were obtained at baseline and a month after initial periodontal treatment. Levels of 8-OHdG were analysed by ELISA.. While plasma 8-OHdG levels were significantly higher at baseline in the obese patients with periodontal disease than in the normal-weight individuals (P<0.05), no significant differences in GCF and saliva 8-OHdG levels were found (P ˃ 0.05). GCF and salivary 8-OHdG levels in obese patients with G and CP were significantly higher than in CTRL groups at baseline (P<0.05). After treatment, 8-OHdG levels were decreased in all groups with periodontal disease (P<0.01). Statistically significant positive correlations were observed between GCF 8-OHdG levels and GI in all the groups (P<0.001).. The significant increase of plasma 8-OHdG levels in obese patients did not correlate with saliva and GCF 8-OHdG levels when compared to normal-weight individuals. Periodontal treatment had a positive effect on the periodontal parameters and 8-OHdG levels of both obese and normal-weight individuals.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Chronic Periodontitis; Deoxyguanosine; Female; Gingival Crevicular Fluid; Gingivitis; Humans; Male; Middle Aged; Obesity; Oxidative Stress; Periodontal Attachment Loss; Reactive Oxygen Species; Saliva

Urinary excretion of the RNA and DNA oxidation markers, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in newly diagnosed adult type 2 diabetics are reported to be long-term predictors of mortality independent of conventional risk factors. In the current study, we investigated the relationships between urinary markers of nucleic acid oxidation concentrations and the degree of obesity and glucose metabolism in overweight compared to lean children. Forty-two (24 girls) overweight and 35 lean (19 girls) children and adolescents were recruited from the Registry of the Danish Childhood Obesity Biobank. Anthropometric measurements were collected at baseline and glucose metabolism was assessed by an oral glucose tolerance test. A urine sample was obtained during the test. Linear regression did not demonstrate any associations between the urinary markers and the degree of obesity or glucose metabolism in lean and obese children. However, sub-analyses adjusted for age, sex, and the degree of obesity showed positive associations between the 2 h glucose and the urinary markers, 8-oxoGuo (p = 0.02, r(2)= 0.63) and 8-oxodG (p = 0.046, r(2)= 0.48), and between the insulinogenic index and 8-oxoGuo (p = 0.03, r(2 )=( )0.60) in the 12 obese children exhibiting impaired glucose tolerance. Excretion of the urinary markers of nucleic acid oxidation and the degree of obesity or the glucose metabolism were not associated in this study. Nevertheless, obese children with impaired glucose tolerance seem to exhibiting an increased oxidative stress level, but due to the small sample size in this study, further investigations are required to elucidate this correlation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Biomarkers; Child; Cross-Sectional Studies; Denmark; Deoxyguanosine; Diabetes Mellitus, Type 2; Female; Guanosine; Humans; Male; Obesity; Oxidative Stress; Pilot Projects

We investigated the effects of a mixture of daidzin and glycitin, which are the glycoside-form isoflavones of daidzein and glycitein, respectively, on body weight, lipid levels, diabetic markers, and metabolism in a high-fat diet (HF) fed C57BL/6J mice for 92 days. The mice were divided into basic diet group (CON), HF group, and HF companied with the isoflavone mixture group (HFISO). Results showed that mice in HFISO had a significantly lower body weight and adipose tissue compared to HF group. Blood glucose, serum HbA1c, and serum insulin also showed lower levels in HFISO group. In addition, higher hepatic GSH level and lower serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) level were found in HFISO group mice. This suggests that the regulation of oxidative stress by daidzin and glycitin was closely related to the suppression of adipose tissue and the progression of diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Deoxyguanosine; Diabetes Mellitus; Diet, High-Fat; Dietary Fats; Glutathione; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Isoflavones; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Oxidative Stress

Metabolic syndrome describes a group of clinical features that together increase the incidence of coronary artery disease, stroke and type 2 diabetes. Insulin resistance is a major risk factor for developing metabolic syndrome. A chronic state of inflammation accompanies the accumulation of surplus lipids in adipose and liver tissue, frequently involved in insulin resistance. 8-Oxo-2'-deoxyguanosine (8-Oxo-dG) is a potent anti-inflammatory agent that inactivates both Rac1 and Rac2 which are critical to initiating the inflammatory responses in various cell types, including macrophages. In this study, we explored whether 8-Oxo-dG suppressed a series of systemic inflammatory cascades, resulting in the amelioration of typical features of metabolic syndrome in obese mice. The results demonstrate that 8-Oxo-dG effectively improved hyperglycemia, dyslipidemia and fatty liver changes in obese mice. The level of biochemical markers indicative of systemic inflammation were reduced in 8-Oxo-dG treated mice, whereas serum levels of adiponectin, a crucial factor associated with improved metabolic syndrome, were enhanced. Our results demonstrate that 8-Oxo-dG effectively disrupts the pathogenesis of insulin resistance and obesity-associated metabolic syndrome.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cytokines; Deoxyguanosine; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Treatment Outcome

Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.. LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls.. Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Benzofurans; C-Reactive Protein; Chemokine CCL2; Deoxyguanosine; Depsides; Diabetic Retinopathy; Glucose; Glucose Intolerance; Insulin Resistance; Male; Obesity; Rats; Rats, Long-Evans; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Over-weight and obesity are serious problems that increase the risk not only for chronic diseases like diabetes and heart disease but also of various types of cancer. This study was conducted to evaluate cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and their relationship with age, body-mass index (BMI) and waist-to-hip ratio (WHR) in 83 obese, 21 over-weight and 21 normal-weight subjects. Frequencies of micronuclei (MN), nucleoplasmic bridges (NPB), nuclear buds (NBUD), and apoptotic and necrotic cells in lymphocytes of obese subjects were found to be significantly higher than those found in normal-weight and over-weight subjects (p<0.01 and p<0.05), whereas plasma concentrations of 8-OHdG in obese subjects were lower than those observed in normal-weight and over-weight subjects (p<0.05 and p<0.01, respectively). There was a negative correlation between age and frequency of necrotic cells and NDI (p<0.05), whereas there was no correlation between BMI, WHR, CBMN cyt assay parameters and plasma 8-OHdG in normal-weight subjects. In over-weight subjects, a negative correlation was observed between age and NDI (p<0.01) and a positive correlation between age and frequency of NPB (p<0.01) and between BMI and frequency of NBUD (p<0.05). In obese subjects, a negative correlation was observed between age and NDI (p<0.01) and between BMI and NDI (p<0.05), whereas no correlation was observed between WHR and CBMN-cyt assay parameters and plasma 8-OHdG. However, frequencies of MN, NPB, NBUD, apoptotic and necrotic cells in total over-weight/obese (p<0.01/p<0.05) and all subjects (p<0.01) increased with increasing BMI. The increase in genomic damage (MN, NPB and NBUD) in obese subjects and the positive correlation between genomic damage and BMI in total over-weight/obese subjects indicate that obesity increases genomic damage and may be associated with an increased risk of cancer, because an increase in MN frequency is a predictor of cancer risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Body Mass Index; Case-Control Studies; Cell Proliferation; Cells, Cultured; Chromosome Aberrations; Deoxyguanosine; DNA Damage; Female; Humans; Male; Micronucleus Tests; Middle Aged; Obesity; Oxidative Stress; Young Adult

The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT.. We studied 149 asymptomatic hypertensive patients (61 ± 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined.. 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-α, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-α were independent factors of 8-OHdG/creatinine.. Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-α is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Blood Pressure; Cardiovascular Diseases; Deoxyguanosine; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Inflammation; Interleukin-6; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Risk Factors; Tumor Necrosis Factor-alpha

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a metabolic syndrome characterized by accumulation of hepatic fat, inflammation and varying degrees of fibrosis. Angiotensin (AT)-II has been reported to play a role in the establishment of NASH. This study examined the effects of an AT-II receptor blocker, irbesartan, on NASH using fatty liver Shionogi (FLS)-ob/ob male mice as the closest animal model of human metabolic syndrome-related NASH. Irbesartan (30 mg/kg/day) was orally administered to FLS-ob/ob mice for 12 weeks (irbesartan group). The effects of irbesartan on steatohepatitis were examined using factors including steatosis, fibrosis, inflammation and oxidative stress. The areas of hepatic fibrosis and hepatic hydroxyproline content were significantly lower in the irbesartan group compared to controls. The areas of α-smooth muscle actin-positivity and F4/80-positive cells were significantly decreased in the irbesartan group. The percentage of 8-hydroxy-2-deoxyguanosine (8-OHdG)-positive cells and 8-OHdG DNA content were significantly decreased in the irbesartan group compared to controls. Levels of RNA expression for procollagen I, transforming growth factor β1, tumor necrosis factor-α, sterol regulatory element-binding protein 1c and fatty acid synthase were significantly lower in the irbesartan group compared to controls. In contrast, the gene expression of peroxisome proliferator activated receptor-α was significantly higher in the irbesartan group compared to controls. Irbesartan administration improved hepatic steatosis and attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Kupffer cells and reducing oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Actins; Angiotensin II Type 1 Receptor Blockers; Animals; Biphenyl Compounds; Collagen Type I; Deoxyguanosine; Fatty Acid Synthases; Fatty Liver; Hepatic Stellate Cells; Inflammation; Irbesartan; Liver Cirrhosis; Male; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; PPAR alpha; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Tetrazoles; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

To correlate changes between VEGF expression with systemic and retinal oxidative stress and inflammation in rodent models of obesity induced insulin resistance and diabetes.. Retinal VEGF mRNA and protein levels were assessed by RT-PCR and VEGF ELISA, respectively. Urinary 8-hydroxydeoxyguanosine (8-OHdG), blood levels of C-reactive protein (CRP), malondialdehyde (MDA), and CD11b/c positive cell ratio were used as systemic inflammatory markers. Retinal expression of Nox2, Nox4, and p47phox mRNA levels were measured as oxidative stress markers. TNF-α, inter-cellular adhesion molecule-1 (ICAM-1), IL1β, and activation of nuclear factor κB (NF-κB) were used as retinal inflammatory markers.. Retinal VEGF mRNA and protein expression increased in Zucker diabetic fatty (ZDF(fa/fa)) rats and streptozotosin (STZ) induced diabetic Sprague-Dawley rats, after two months of disease, but not in Zucker fatty (ZF) rats. Systemic markers of oxidative stress and inflammation were elevated in insulin resistant and diabetic rats. Some oxidative stress and inflammatory markers (TNF-α, IL-6, ICAM-1, and IL1-β) were upregulated in the retina of ZDF(fa/fa) and STZ diabetic rats after 4 months of disease. In contrast, activation of NF-κB in the retina was observed in high fat fed nondiabetic and diabetic cis-NF-κB(EGFP) mice, ZF, ZDF(fa/fa), and STZ-induced diabetic rats.. Only persistent hyperglycemia and diabetes increased retinal VEGF expression. Some markers of inflammation and oxidative stress were elevated in the retina and systemic circulation of obese and insulin resistant rodents with and without diabetes. Induction of VEGF and its associated retinal pathologies by diabetes requires chronic hyperglycemia and factors in addition to inflammation and oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; C-Reactive Protein; CD11b Antigen; CD11c Antigen; Deoxyguanosine; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Inflammation; Insulin Resistance; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; NF-kappa B; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rats, Zucker; Retina; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stress, Physiological; Vascular Endothelial Growth Factor A

Diabetic nephropathy is characterized by abnormal angiogenesis, and this is driven by several factors, including hyperglycaemia and ischaemia. We investigated the role of vascular endothelial growth factor receptor-2 (VEGFR-2) blockade and its effects on diabetic nephropathy.. Male db/db and db/m mice received long-term treatment with dRK6, an arginine-rich anti-VEGF hexapeptide, for 12 weeks or short-term treatment for only the first 4 weeks, starting from 8 weeks of age.. The urinary albuminuria and VEGF excretion varied according to the duration of diabetes, and the urinary VEGF levels were strongly correlated with the levels of albuminuria. Diabetes increased the VEGFR-2 expression in the kidneys. At the end of the 12-week study, compared with the db/db control mice, the db/db mice with long-term dRK6 treatment, which selectively inhibited VEGFR-2, had more albuminuria, related to weak nephrin signalling and advanced renal phenotypes, which were associated with hypoxia-oxidative stress, and an increased number of apoptotic endothelial cells. Interestingly, these changes were related to a decrease in phospho-Akt/eNOS-NO bioavailability. On the in vitro study, dRK6 increased the number of apoptotic human umbilical vein endothelial cells (HUVECs) in the high glucose media by blocking phospho-Akt/eNOS-NO signalling, and this was related to the increased oxidative stress. The short-term inhibition of VEGFR-2 neither improved the albuminuria nor the renal phenotype induced by diabetes.. Long-term selective blockade of VEGFR-2 by dRK6 had deleterious renal effects, and this was associated with downregulation of the Akt/eNOS-NO axis in db/db mice. Short-term VEGFR-2 blockade did not improve the renal phenotypes and the albuminuria. These findings suggest that VEGF-A-VEGFR-2 inhibition, regardless of how long it may be, does not ameliorate diabetic nephropathy in type 2 diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Animals; Apoptosis; Blotting, Western; Cell Proliferation; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endothelium, Vascular; Immunoenzyme Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nitric Oxide; Nitric Oxide Synthase Type III; Obesity; Oligopeptides; Proto-Oncogene Proteins c-akt; Renal Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

The aim of this study was to investigate the relationship between metabolic risk factors and oxidative stress using urinary 8-hydroxydeoxyguanosine (8-OHdG), a recently utilized biological marker, in asymptomatic subjects.. Ninety subjects (males/females = 30/60; mean age = 52 years), who were nonsmoking, nondiabetic and not on any medicine, were enrolled in the study. The body mass index, blood pressure, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and glucose as well as urinary 8-OHdG and creatinine were measured.. The median level of 8-OHdG was 9.3 ng/mg creatinine (interquartile range: 5.8-23.2). TG (Pearson's correlation: r = 0.262, p = 0.013) and HDL-C (r = -0.259, p = 0.014) showed a significant correlation with 8-OHdG. A multiple linear regression analysis adjusted for all the variables revealed that only TG had an independently significant and positive correlation with 8-OHdG (β = 0.231, p = 0.046).. The data in this population suggest that, among metabolic risk factors, hypertriglyceridemia may be weakly but significantly associated with hyperoxidative stress as assessed by 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Blood Pressure; Body Mass Index; Cholesterol, HDL; Deoxyguanosine; Female; Humans; Linear Models; Male; Middle Aged; Obesity; Oxidative Stress; Risk Factors; Statistics, Nonparametric; Triglycerides

The purpose of the present study was to investigate the effects of exercise training on serum reactive oxygen species (ROS) level and gingival oxidative stress in obese rats fed a high-fat diet.. Rats were divided into three groups (n = 14/group): one control group (fed a regular diet) and two experimental groups (fed a high-fat diet with and without exercise training [treadmill: 5 days/week]). The rats were sacrificed at 4 or 8 weeks. The level of serum reactive oxidative metabolites (ROM) was measured as an indicator of circulating ROS. The level of 8-hydroxydeoxyguanosine (8-OHdG) and reduced-form glutathione (GSH)/oxidised-form glutathione (GSSG) ratio were determined to evaluate gingival oxidative stress.. The obese rats fed a high-fat diet without exercise training showed higher serum ROM levels [Carratelli Units (CARR U)] (mean ± SD; 413 ± 64) than the control (333 ± 12) at 4 weeks (p = 0.023). Such a condition resulted in higher 8-OHdG levels (ng/mg mtDNA) (0.97 ± 0.18) (p < 0.05) and a lower GSH/GSSG ratio (17.0 ± 3.1) (p < 0.05) in gingival tissues, compared to the control (0.55 ± 0.13 for 8-OHdG and 23.6 ± 5.8 for GSH/GSSG ratio) at 8 weeks. In addition, the obese rats fed a high-fat diet with exercise training showed lower serum ROM (623 ± 103) (p < 0.001) and gingival 8-OHdG levels (0.69 ± 0.17) (p = 0.012) than those without exercise training (1105 ± 95 for ROM and 0.55 ± 0.13 for 8-OHdG) at 8 weeks.. Obesity prevention by exercise training may effectively suppress gingival oxidative stress by decreasing serum ROS in rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acid Phosphatase; Alveolar Bone Loss; Animals; Biomarkers; Body Weight; C-Reactive Protein; Connective Tissue; Deoxyguanosine; Dietary Fats; Gingiva; Glutathione; Glutathione Disulfide; Intra-Abdominal Fat; Isoenzymes; Male; Neutrophils; Obesity; Osteoclasts; Oxidative Stress; Periodontal Ligament; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Subcutaneous Fat; Tartrate-Resistant Acid Phosphatase

This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls.. Participants attended the School of Community Health, Diabetes Screening Clinic, Charles Sturt University, Australia, between February 2006 and June 2008. A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds.. Serum 8-hydroxy 2'-deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3±140 pg/ml) compared with controls (210.1±166 pg/ml; P<0.01). The diabetic group (1979.6±1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5±103 pg/ml; P<0.001) and overweight subjects (724±102 pg/ml; P=0.005) compared with the lean subjects (196.5±327 pg/ml).. Our results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol, HDL; Deoxyguanosine; Diabetes Mellitus, Type 2; DNA Damage; Female; Free Radicals; Glycated Hemoglobin; Humans; Lipids; Male; Middle Aged; Multivariate Analysis; Obesity; Oxidative Stress; Prediabetic State; Sex Characteristics

Obesity-related metabolic abnormalities, including chronic inflammation and oxidative stress, increase the risk of colorectal cancer. Dysregulation of the renin-angiotensin system (RAS) also plays a critical role in obesity-related metabolic disorders and in several types of carcinogenesis. In the present study, we examined the effects of an angiotensin-converting enzyme (ACE) inhibitor and angiotensin-II type 1 receptor blocker (ARB), both of which inhibit the RAS, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were given 4 weekly subcutaneous injections of AOM (15 mg/kg body weight), and then, they received drinking water containing captopril (ACE inhibitor, 5mg/kg/day) or telmisartan (ARB, 5mg/kg/day) for 7 weeks. At sacrifice, administration of either captopril or telmisartan significantly reduced the total number of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, compared to that observed in the control group. The expression levels of TNF-α mRNA in the colonic mucosa of AOM-treated db/db mice were decreased by captopril and telmisartan. Captopril lowered the expression levels of TNF-α, IL-1β, IL-6, and PAI-1 mRNAs, while telmisartan lowered the expression levels of COX-2, IL-1β, IL-6, and PAI-1 mRNAs in the white adipose tissues of these mice. In addition, these agents significantly reduced the levels of urinary 8-OHdG, a surrogate marker of oxidative damage to DNA, in the experimental mice. These findings suggested that both ACE inhibitor and ARB suppress chemically-induced colon carcinogenesis by attenuating chronic inflammation and reducing oxidative stress in obese mice. Therefore, targeting dysregulation of the RAS might be an effective strategy for chemoprevention of colorectal carcinogenesis in obese individuals.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Azoxymethane; Benzimidazoles; Benzoates; Captopril; Colonic Neoplasms; Cyclooxygenase 2; Deoxyguanosine; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Oxidative Stress; Plasminogen Activator Inhibitor 1; Precancerous Conditions; Renin-Angiotensin System; RNA, Messenger; Telmisartan; Tumor Necrosis Factor-alpha

Advanced glycation end products (AGEs) contribute to the pathogenesis of diabetes-associated complications. Previously, we reported the possible effect of pyridoxamine (K-163), an AGE inhibitor, on improvement of glucose intolerance in type 2 diabetes mellitus KK-A(y)/Ta mice. Recently, AGEs and oxidative stress have been shown to induce insulin resistance. The objective of the present study is to examine the effect of pyridoxamine on glucose intolerance and oxidative stress. C57BL/6J mice were divided into 3 groups as follows: low-fat diet, high-fat diet, and high-fat diet with pyridoxamine treatment. Body and adipose tissue weight, serum insulin, hydrogen peroxide, malondialdehyde and AGE, and urinary 8-hydroxy-2'-deoxyguanosine levels were measured. Nicotinamide adenine dinucleotide phosphate subunits, antioxidant enzymes, and adipocytokine messenger RNA expressions in the adipose tissues were evaluated. Akt/protein kinase B activity and glucose transporter 4 translocation in skeletal muscle were also evaluated. Body and adipose tissue weights of the pyridoxamine treatment group were significantly decreased compared with those of the high-fat diet group. Pyridoxamine attenuated serum hydrogen peroxide, malondialdehyde and AGE, and urinary 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase expression; increased antioxidant enzyme expression; and improved dysregulation of adipocytokines in adipose tissues. Pyridoxamine improved blood glucose levels after glucose injection and fasting hyperinsulinemia. Suppressed Akt/protein kinase B activity and glucose transporter 4 translocation in skeletal muscle in high-fat diet mice were improved by pyridoxamine treatment. It appears that the antioxidative effect of pyridoxamine is associated with improvement of glucose intolerance and obesity in C57BL/6J mice fed a high-fat diet. We assume that pyridoxamine may be useful in the treatment of the obesity-associated metabolic syndrome.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adipokines; Adipose Tissue; Animals; Antioxidants; Cholesterol; Deoxyguanosine; Dietary Fats; Glucose Intolerance; Glycation End Products, Advanced; Hydrogen Peroxide; Immunohistochemistry; Malondialdehyde; Mice; Mice, Inbred C57BL; Muscle, Skeletal; NADPH Oxidases; Obesity; Pyridoxamine; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Superoxide Dismutase; Triglycerides

The aim of the present observational study was to investigate the relationships between glycaemic status and levels of oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Metabolic variables (weight, BMI, waist circumference (waist), blood glucose, glycated Hb (HbA(1c)), insulin, blood lipids), biomarkers of oxidative stress (8-iso-PGF(2alpha), malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, formamido pyrimidine glycosylase-sites, frequency of micronucleated erythrocytes, nitrotyrosine) and inflammatory markers (high sensitivity C-reactive protein (hsCRP), IL-6, cyclo-oxygenase-catalyzed PGF(2alpha)-metabolite) were measured. Fifty-six patients (thirty women and twenty-six men, age 62.3 (SD 7.0) years, HbA(1c) 6.1 (SD 0.9) %, BMI 28.3 (SD 3.8) kg/m(2), waist 99.6 (SD 11.1) cm) were included in the study. HbA(1c) (r 0.29, P=0.03) and blood glucose (r 0.33, P=0.01) correlated positively with 8-iso-PGF(2alpha). Positive correlations were also observed between HbA(1c) and nitrotyrosine (r 0.42, P=0.01), waist and hsCRP (r 0.37, P=0.005), hsCRP and IL-6 (r 0.61, P<0.0001) and between PGF(2alpha)-metabolite and 8-iso-PGF(2alpha) (r 0.27, P=0.048). The present study indicates that glycaemic status is associated with oxidative stress even in subjects with well-controlled type 2 diabetes. Furthermore, inflammation was more related to abdominal obesity than to glycaemic control. A large number of biomarkers of oxidative stress and inflammation were investigated, but only a few associations were found between the markers. This could be due to the fact that none of these biomarkers biosynthesises via similar pathways or simultaneously owing to their diverse nature and origin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Deoxyguanosine; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-6; Lipids; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Probability; Statistics, Nonparametric; Tyrosine; Waist Circumference

Studies indicate a correlation between obesity and periodontitis. Oxidative stress is involved in the progression of periodontitis. The purpose of this study was to investigate the effects of obesity on gingival oxidative stress in a rat periodontitis model.. The obese Zucker rats (n = 14) and their lean littermates (n = 14) were each divided into two groups of seven rats. In one of each group, periodontitis was induced by ligature for 4 weeks, whereas the other group was left unligated. The level of 8-hydroxydeoxyguanosine and the ratio of reduced/oxidized glutathione were determined to examine gingival oxidative stress. The serum level of reactive oxygen metabolites and the gingival gene-expression pattern related to oxidative/metabolic stress, inflammation, and cell behavior were also evaluated.. The obese rats weighed more than the lean rats at 4 weeks. Compared to lean rats, obese rats had enhanced gingival 8-hydroxydeoxyguanosine levels and a decreased ratio of reduced/oxidized glutathione in the gingival tissue, with increasing serum reactive oxygen metabolites. However, there were no significant differences in the degree of alveolar bone loss between lean and obese rats, except for teeth with and without ligatures in both rats. In addition, the periodontal lesion in obese rats showed higher 8-hydroxydeoxyguanosine levels and polymorphonuclear leukocyte infiltration than the inflamed ones in lean rats, with downregulation of multiple cytochrome P450 gene expression.. Obesity induced gingival oxidative stress with increasing serum reactive oxygen metabolites in rats. In the periodontal lesion, gene expressions related to a capacity for xenobiotic detoxification were downregulated in the obese model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alveolar Bone Loss; Animals; Body Weight; Cytochrome P-450 Enzyme System; Deoxyguanosine; Disease Models, Animal; Down-Regulation; Gingiva; Gingivitis; Glutathione; Leukocyte Count; Male; Neutrophils; Obesity; Oxidation-Reduction; Oxidative Stress; Periodontitis; Rats; Rats, Zucker; Reactive Oxygen Species

Medications to treat hyperglycemia and hyperinsulinemia are expected to inhibit the accumulation of advanced glycation end-products in the diabetic kidney and improve renal function by inhibiting oxidative reactions. In this study, we examined the effect of pioglitazone, an insulin sensitizer, on diabetic nephropathy. Feed containing pioglitazone at 0.01 or 0.02% was given to Zucker-fatty rats for 27 weeks. Pioglitazone reduced plasma glucose, plasma insulin, and blood HbAlc levels. It also decreased plasma total cholesterol, triglyceride, phospholipid and cystatin C levels and inhibited the increase in urine of 8-hydroxydeoxyguanosine and in plasma of malondialdehyde. In the histopathological examinations, pioglitazone inhibited diffusive or nodular thickening of the mesangial matrix, atrophy of the proximal convoluted tubule, thickening of the basement membrane of the tubule, and mild cellular infiltration (mostly small lymphocytes) in the stroma. Furthermore, pioglitazone inhibited the mRNA expression of the receptor for advanced glycation end-products (RAGE) and that of transforming growth factor-beta. Long-term administration of pioglitazone improved hyperglycemia lipid profiles, hypercholesterolemia, and hyperinsulinemia and had a protective effect on diabetic nephropathy in Zucker-fatty rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Cholesterol; Cystatin C; Cystatins; Diabetic Nephropathies; Glycated Hemoglobin; Guanine; Hypoglycemic Agents; Insulin; Kidney; Malondialdehyde; Obesity; Oxidation-Reduction; Phospholipids; Pioglitazone; Rats; Rats, Zucker; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Thiazolidinediones; Transforming Growth Factor beta; Triglycerides

Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance.. During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-alpha, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66-101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-alpha and IL-6) were obtained.. 8OHdG was higher in WG compared with WM (149.1+/-16.2 versus 117.8+/-29.5, P=0.03), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9+/-7.6 versus 9.8+/-6.3) but noticeably higher in elderly subjects (21.5+/-15.3, P=0.059). TNF-alpha protein in WG was higher compared with WM (114.0+/-41.7 versus 70.1+/-23.3, P=0.025), and was associated with weight increase.. Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Aging; Aldehydes; Case-Control Studies; Deoxyguanosine; DNA Damage; Humans; Immunohistochemistry; Inflammation; Male; Middle Aged; Muscle, Skeletal; Obesity; Tumor Necrosis Factor-alpha; Weight Gain