Cross-sectional and longitudinal associations of PAHs exposure with serum uric acid and hyperuricemia among Chinese urban residents: The potential role of oxidative damage.

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-µmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 µmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.

Micronuclei and other nuclear anomalies in exfoliated urothelial cells and urinary 8-hydroxy-deoxyguanosine levels among Turkish hairdressers.

Hairdressers are constantly occupationally exposed to many chemicals have the potential to cause allergies and carcinogenic effects, act as skin and eye irritants and induce oxidative stress and DNA damage. This study aimed to evaluate occupation-induced genotoxicity based on the presence of micronucleus (MN) and other nuclear anomalies in urothelial cells and measure oxidative DNA damage based on the 8-hydroxy-2'-deoxyguanosine level in the urine of Turkish hairdressers. Originality of this study comes from that there was no study on MN and other nuclear anomalies frequencies and oxidative DNA damage in urine samples of hairdressers in the literature. The mean±standard deviation frequency (‰) of micronucleated (MNed) cells was higher in the hairdresser group (n=56) (4.81±7.87, p<0.001) than in the control group (n=56) (0.93±1.85). Nuclear buds were not observed in either group. While the frequency of basal cells was higher in the control group (446.6±106.21) than in the hairdresser group (367.78±101.51, p<0.001), the frequency of binuclear, karyolytic, pycnotic and karyorrhectic cells were higher in the hairdresser group (0.41±0.80, p<0.001; 438.02±118.27, p<0.001; 0.43±0.76, p<0.001; and 47.27±28.40, p<0.001) than in the control group (0.04±0.27, 358.57±95.71, 0.05±0.23 and 24.41±14.50). Condensed chromatins were observed only in the hairdresser group. Specific gravity adjusted 8-hydroxy-2'-deoxyguanosine level was statistically lower in the hairdresser group (908.21±403.25 ng/mL-SG) compared to the control group (1003.09±327.09 ng/mL-SG) (p=0.024). No significant correlation was found between the 8-hydroxy-2'-deoxyguanosine level and the frequency MN. The amount of formaldehyde released during Brazilian keratin treatment was higher than the American Conference of Governmental Industrial Hygienists -Threshold Limit Value (ACGIH-TLV; 0.1 ppm). Similarly, the amount of ethyl acetate released in three salons was above the recommended limit (400 ppm). These findings suggest that hairdressers have an increased risk of genotoxicity and cytotoxicity owing to occupational exposure, regardless of age, working hours, smoking and alcohol consumption.

The effect of smoking on clinical and biochemical early healing outcomes of coronally advanced flap with connective tissue graft: Prospective cohort study.

BACKGROUND: This study aimed to determine the effects of smoking on early (≤3 months) clinical outcomes and relevant molecular biomarkers following root coverage surgery. METHODS: Eighteen smokers and 18 nonsmokers, status biochemically verified, with RT1 gingival recession defects were recruited and completed study procedures. All patients received coronally advanced flap plus connective tissue graft. Baseline and 3 month recession depth (RD), recession width (RW), keratinized tissue width (KTW), clinical attachment level (CAL), and gingival phenotype (GP) were recorded. Root coverage (RC) percentage and complete root coverage (CRC) were calculated. Recipient (gingival crevicular fluid) and donor (wound fluid) site VEGF-A, HIF-1α, 8-OHdG, and ANG levels were determined. RESULTS: There were no significant intergroup differences for any baseline or postoperative clinical parameters (P > 0.05), except for whole mouth gingival index (increased in nonsmokers at 3 months; P < 0.05). Compared to baseline, RD, RW, CAL, KTW, and GP significantly improved postoperatively, without significant intergroup differences. There were no significant intergroup differences for RC (smokers = 83%, nonsmokers = 91%, P = 0.069), CRC (smokers = 50%, nonsmokers = 72%, P = 0.177), and CAL gain (P = 0.193). The four biomarker levels significantly increased postoperatively (day 7; P ≤ 0.042) in both groups and returned to baseline (day 28) without significant intergroup differences (P > 0.05). Similarly, donor site parameters were not different between groups. Strong correlations, consistent over time, were found between biomarkers implicated in angiogenesis (VEGF-A, HIF-1α, and ANG). CONCLUSIONS: The early (3 month) clinical and molecular changes after root coverage surgery utilizing a coronally advanced flap plus connective tissue graft are similar between smokers and nonsmokers.

Toxicity comparison of atrazine on Eisenia fetida in artificial soil and three natural soils.

Atrazine has been widely used in the world and caused environmental pollution, especially soil pollution. When assessing the toxicity of atrazine in soil, most studies used standardized artificial soils, while few studies focused on the real soil environments. In the present study, three natural soils and artificial soil were selected as test soils to study and compare the toxicities of atrazine to Eisenia fetida. Acute toxicity of atrazine was determined by filter paper and soil tests. In chronic toxicity study, after atrazine exposure, the content of reactive oxygen species in Eisenia fetida significantly increased and showed a dose-response relationship. The activity changes of three antioxidant enzymes and glutathione transferase showed that atrazine had obvious oxidative stress effect on earthworms. The contents of malondialdehyde and 8-hydroxy deoxyguanosine in 0.1 and 1 mg/kg atrazine treatment groups were significantly higher than the control, indicating that medium and high concentrations of atrazine could cause lipid and DNA damage in Eisenia fetida. The acute toxicity results and the integrated biomarker response index for chronic toxicity indicated that the toxicity order of atrazine was: red clay > fluvo-aquic soil > artificial soil > black soil, and that the toxicity of atrazine in artificial soil was not representative of its toxicity in real soil environment. The results of correlation analysis showed that three soil property parameters of organic carbon, organic matter and sand were most related to the toxicity of atrazine.

Effects of Nonsurgical Periodontal Therapy on Salivary 8-Hydroxy-Deoxyguanosine Levels and Glycemic Control in Diabetes Mellitus Type 2 Patients.

Diabetes and periodontitis are complex chronic diseases that are potentially interrelated, as well as associated with oxidative stress. Thus, the aim of the present study was to evaluate the influence of nonsurgical periodontal treatment on salivary 8-hydroxy-deoxyguanosine (8-OHdG) levels and glycemic control in patients suffering from both diabetes mellitus type 2 (DM2) and periodontitis. The study sample included 53 DM2 patients, while 31 systemically healthy patients served as controls. Participants in both groups suffered from periodontitis of comparable severity. Periodontal clinical parameters, namely plaque index (PI), gingival index (GI), papilla bleeding index (PBI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded, along with salivary 8-OHdG levels and glycated hemoglobin (HbA1c). Levels of 8-OHdG were analyzed by ELISA. All aforementioned parameters were evaluated prior to commencing the study and at 90-day follow-up upon nonsurgical periodontal therapy completion. At baseline, salivary levels of 8-OHdG in DM2 patients were significantly higher (1.17 ng/mL) than those measured for the control group (0.75 ng/mL) and showed significant positive correlation with GI and PPD (p < 0.05). Three months after nonsurgical periodontal therapy, the salivary 8-OHdG levels were significantly reduced in DM2 patients (p < 0.05). Analysis results also revealed statistically significant changes in all measured clinical parameters between baseline and three-month follow-up in both groups (p < 0.05). Upon treatment completion, a decline in the HbA1c level was noted in DM group, but it did not reach statistical significance (p > 0.05). It can be concluded that DM2 patients benefit from non-surgical periodontal therapy, as indicated by a marked reduction in their salivary 8-OHdG level and a modest improvement in glycemic control. Short-term clinical benefits noted in the DM group were similar to those observed in the non-diabetic periodontal patients.

Association between lead exposure and DNA damage (genotoxicity): systematic review and meta-analysis.

Studies suggest that chronic lead (Pb) exposure may induce deoxyribonucleic acid (DNA) damage. However, there is no synthesised evidence in this regard. We systematically reviewed existing literature and synthesised evidence on the association between chronic Pb exposure and markers of genotoxicity. Observational studies reporting biomarkers of DNA damage among occupationally Pb-exposed and unexposed controls were systematically searched from PubMed, Scopus and Embase databases from inception to January 2022. The markers included were micronucleus frequency (MN), chromosomal aberrations, comet assay, and 8-hydroxy-deoxyguanosine. During the execution of this review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Mean differences in the biological markers of DNA damage between Pb-exposed and control groups were pooled using the random-effects model. The heterogeneity was assessed using the Cochran-Q test and I2 statistic. The review included forty-five studies comparing markers of DNA damage between Pb-exposed and unexposed. The primary studies utilised buccal and/or peripheral leukocytes for evaluating the DNA damage. The pooled quantitative results revealed significantly higher DNA damage characterised by increased levels of MN and SCE frequency, chromosomal aberrations, and oxidative DNA damage (comet assay and 8-OHdG) among Pb-exposed than the unexposed. However, studies included in the review exhibited high levels of heterogeneity among the studies. Chronic Pb exposure is associated with DNA damage. However, high-quality, multicentred studies are required to strengthen present observations and further understand the Pb's role in inducing DNA damage. CRD42022286810.

Synergistic effect of curcumin and chitosan nanoparticles on nano-hydroxyapatite-induced reproductive toxicity in rats.

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (HAPNPs), a prospective nano-biomaterial, is extensively studied, its interaction on the reproductive system following exposure is less exploited. In the present study, male rats were exposed to HAPNPs (300 mg/kg BW) to determine its possible reproductive toxicity. Also, the protective effects of chitosan (CSNPs, 280 mg/kg BW) and/or curcumin (CurNPs, 15 mg/kg BW) nanoparticles against HAPNPs-induced reproductive toxicity were studied. Animals were orally gavage daily with respective doses for 45 consecutive days. The obtained results indicated that HAPNPs caused a significant decrease in sperm count, sperm motility, testosterone hormone, steroidogenic enzymes (17-ketosteroid reductase and 17ß-hydroxysteroid dehydrogenase), and antioxidant enzymes (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase) in addition to total antioxidant capacity and reduced glutathione. LH and FSH, abnormal sperm, oxidative stress parameters (thiobarbituric acid-reactive substances (TBARS), nitric oxide (NO), and 8-hydroxy-deoxyguanosine (8-OHdG)), p53, TNFα, and interleukin-6 were significantly increased. The DNA damage was also analyzed by assaying 8-OHdG level which is considered as an indicator of genotoxicity and also suppression of the gene expression of mtTFA, induction of UCP2. Similarly, the histopathological evaluation was also changed following exposure to HAPNPs. The antioxidant activity of CSNPs and CurNPs showed mitigating effect against reproductive deterioration induced by HAPNPs throughout improvements in semen characteristics, sex hormones, inflammatory factors, and antioxidant status. The present study concluded that HAPNPs induced reproductive toxicity and it is important to use nano-antioxidants CSNPs and CurNPs as protective agents.

The flavoring and not the nicotine content is a decisive factor for the effects of refill liquids of electronic cigarette on the redox status of endothelial cells.

Electronic cigarettes are constantly gaining ground as they are considered less harmful than conventional cigarettes, and there is also the perception that they may serve as a potential smoking cessation tool. Although the acute effects of electronic cigarette use have been extensively studied, the long-term potential adverse effects on human health remain largely unknown. It has been well-established that oxidative stress is involved in the development of various pathological conditions. So far, most studies on e-cigarettes concern the effects on the respiratory system while fewer have focused on the vascular system. In the present study, we attempted to reveal the effects of electronic cigarette refill liquids on the redox state of human endothelial cells (EA.hy926 cell line). For this purpose, the cytotoxic effect of three e-liquids with different flavors (tobacco, vanilla, apple/mint) and nicotine concentrations (0, 6, 12, 18 mg/ml) were initially examined for their impact on cell viability of EA.hy926 cells. Then, five redox biomarkers [reduced form of glutathione (GSH), reactive oxygen species (ROS), total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyls (CARBS)] were measured. The results showed a disturbance in the redox balance in favor of free radicals in tobacco flavored e-liquids while vanilla flavored e-liquids exhibited a more complex profile depending on the nicotine content. The most interesting finding of the present study concerns the apple/mint flavored e-liquids that seemed to activate the cellular antioxidant defense and, thus, to protect the cells from the adverse effects of free radicals. Conclusively, it appears that the flavorings and not the nicotine content play a key role in the oxidative stress-induced toxicity of the e-liquids.

Prognostic impact of 8-hydroxy-deoxyguanosine and its repair enzyme 8-hydroxy-deoxyguanosine DNA glycosylase in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.

Urinary 8-hydroxydeoxyguanosine in relation to XRCC1 rs25487 G/A (Arg399Gln) and OGG1 rs1052133 C/G (Ser326Cys) DNA repair genes polymorphisms in patients with chronic hepatitis C and related hepatocellular carcinoma.

Background and aim: DNA repair represents a protective mechanism against cell injury and cancer. 8-hydroxy-deoxyguanosine (8-OHdG) is the main ROS-induced DNA mutation. The current study aimed to evaluate urinary 8-OHdG levels in patients with chronic hepatitis C virus (HCV) and its related hepatocellular (HCC) and correlate its level to XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms. Materials and methods: Urinary 8-OHdG assays were performed using HPLC technique, and XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms were analyzed by PCR using confronting two-pair primer method (PCR-CTPP) in 200 subjects allocated into 50 chronic HCV patients, 50 HCV-related HCC patients, and 100 controls. Results: There were significantly increased urinary 8-OHdG levels in HCV-related HCC and chronic HCV patients when compared with the controls (P<0.05 for all). Urinary 8-OHdG was associated with the tumor spread. Regarding, XRCC1 (Arg399Gln), AA (Gln/Gln) genotype and A-allele were more frequent in HCC and chronic HCV patients than in the controls (P<0.05). ORs (95%CI) using the dominant and the recessive genetic models were; 2.1 (1.1-4.1), P=0.032 and 1.9 (1-3.6), P=0.043 respectively. For OGG1 (Ser326Cys), GG (Cys/Cys) genotype and G-allele were increased significantly in chronic HCV and HCC patients compared to the controls (P<0.05). ORs (95%CI) under the dominant and the recessive genetic models were; 2.1 (1.1-4.1), P=0.032 and 1.9 (1-3.8), P=0.049 respectively. Additionally, XRCC1 (AA) and OGG1 (GG) genotypes had significantly increased urinary 8-OHdG levels among patients (P<0.05). Conclusions: XRCC1 (AA) and OGG1 (GG) could be considered as possible genotypic risk factors for HCV- related HCC development which were associated with significantly high urinary 8-hydroxy-deoxyguanosine levels, thus urinary 8-OHdG could be considered as non-invasive marker in follow-up chronic HCV progression into HCC.

Deterioration of semen quality and sperm-DNA integrity as influenced by cigarette smoking in fertile and infertile human male smokers-A prospective study.

In modernized lifestyle smoking is one of the trendy, psychological, and socioeconomic scenarios of young adolescents mainly in the age of the reproductive stage. Based on a number of cigarettes smoked, age, and duration of the smoke, the study aims to search for the profound effects of smoking and its impact on semen parameters, sperm-DNA integrity, and fragmentation of sperm DNA with cotinine and apoptotic caspase-3 marker in the seminal plasma of fertile and infertile smokers. To determine oxidative damage by 8-hydroxy deoxyguanosine (8-OHdG) from isolated sperm DNA (steps: reactive oxygen species washing by nitro blue tetrazolium (NBT), sperm lysis, salt digestion, ethanol washing, and finally with high-performance liquid chromatography analysis). Level of DNA fragmentation (percentage) in native and intact DNA, the activity of caspase-3 in infertile smokers will be compared with the control group of nonsmokers. Also, the sperm viability was visualized by eosin-nigrosin and aniline blue staining. Cotinine is one of the best markers of smoking. The cotinine level (2224.24 ± 1.19 *** ng/mL), when abundant it negative correlates with morphology and rapid motility in infertile smokers than nonsmokers. Gel preprogram measured the sperm integrity and was found to be less in smokers than nonsmokers. The spermatic oxidative marker 8-OHdG was high and gave an R 2 value of 0.9104 with morphology and 0.9007 for rapid motility of infertile sperm, respectively. Infertile smoking subjects (<10 cigarettes/day) had significant changes increase in sperm fragmentation, caspase-3, and cotinine while negative impact with motility, morphology, and pH of semen compared with fertile, infertile nonsmoking subjects.

Trichloroethylene exposure in mid-pregnancy decreased fetal weight and increased placental markers of oxidative stress in rats.

Although epidemiology studies have associated maternal trichloroethylene (TCE) exposure with decreased birth weight and preterm birth, mechanistic explanations for these associations are currently lacking. We hypothesized that TCE targets the placenta with adverse consequences for pregnancy outcomes. Pregnant Wistar rats were exposed orally to vehicle or 480 mg TCE/kg body weight from gestational days (gd) 6-16, and tissues were collected on gd 16. Exposure to TCE significantly decreased average fetal weight without reducing maternal weight. In placenta, TCE significantly increased 8-hydroxy-deoxyguanosine, global 5-hydroxymethylcytosine, and mRNA expression of Tet3, which codes for an enzyme involved in 5-hydroxymethylcytosine formation. Furthermore, glutathione S-transferase activity and immunohistochemical staining were increased in placentas of TCE-exposed rats. The present study provides the first evidence that TCE increases markers of oxidative stress in placenta in a fetal growth restriction rat model, providing new insight into the placenta as a potentially relevant target for TCE-induced adverse pregnancy outcomes.

SIRT6 expression and oxidative DNA damage in individuals with prediabetes and type 2 diabetes mellitus.

Sirtuins (SIRTs) is a family of NAD+ dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). SIRT6 gene expression was determined in peripheral blood leukocytes of 70 patients with type 2 diabetes, 50 cases in prediabetic stage and 40 healthy subjects. SIRT6 mRNA levels were determined by quantitive real time- polymerase chain reaction. SIRT6 protein was detected by immunocytochemical staining. Urinary 8-hydroxy deoxyguanosine (8-OHdG) levels were measured by ELISA. There was no significant difference between groups for SIRT6 mRNA level. SIRT6 immunopositivity in T2DM group was lower when compared to those in preDM group (P<0.05). SIRT6 positive cell number in T2DM and preDM groups were lower in comparison to control group (P<0.01 for both), however, when study groups were subdivided into two groups according to their age, the difference between preDM and control groups disappeared in both mid-aged and old-aged groups. The urinary 8-OHdG level was found to be higher in the T2DM group in comparison to preDM group (P<0.05). When age is taken into consideration, urinary 8-OHdG level in the T2DM group was found to be higher than those in both preDM and control groups in the old-aged cases but no significant difference was determined between groups in the mid-aged cases. There was no relation between SIRT6 expression and urinary 8-OHDG excretion. It was concluded that SIRT6 may take play in development of T2DM but this effect seems to be independent from repair of oxidative DNA damage.

Relationship of PAHs metabolites,DNA oxidative damage and RING2 expression in coke oven workers / 中国职业医学

OBJECTIVE: To investigate the relationship of polycyclic aromatic hydrocarbons( PAH) metabolites,DNA oxidative damage and ring finger protein 2( RING2) expression in coke oven workers. METHODS: A judgment sampling method was used to select 497 coke oven workers in a steel plant as exposure group and 175 water treatment workers in the same plant as control group. The levels of urinary 1-hydroxypyrene, 2-hydroxynathalene, 2-hydroxyfluorene,9-hydroxyphenanthrene and 8-hydroxy deoxyguanosine(8-OHd G) were detected by high performance liquid chromatography.The RING2 expression in whole blood was measured by reverse transcription-polymerase chain reaction. RESULTS: The relative expression of urinary 1-hydroxypyrene,2-hydroxynathalene,2-hydroxyfluorene,9-hydroxyphenanthrene and RING2 in exposure group were higher than that in control group( P < 0. 01). The logistic regression analysis indicated that the higher the level of 1-hydroxypyrene,the higher the risk of high-RING2 expression( P < 0. 05) after adjusting for factors such as sex,age,smoking status,alcohol drinking,2-hydroxynathalene,2-hydroxyfluorene and 9-hydroxyphenanthrene.In 1-hydroxypyrene middle and high level groups,the 8-OHd G concentration of high-RING2 expression workers was significantly higher than those of low-RING2 expression workers( P < 0. 05). CONCLUSION: With the increase of urinary1-hydroxypyrene,the risk of high-RING2 expression was elevated,the degree of DNA oxidative damage was gradually increased.

Estimation of 8-Hydroxy-deoxyguanosine (8-OHdG) in Saliva as a Marker of Oxidative Stress in Patients with Chronic Periodontitis: Preliminary Data.

BACKGROUND: This preliminary study assesses the effects of initial periodontal treatment on salivary levels of 8-hydroxy-deoxyguanosine (8-OHdG) as a marker of oxidative stress in patients with chronic periodontitis (CP). METHODS: At baseline, clinical parameters and saliva samples were obtained from 20 patients with CP and 10 patients with clinically healthy periodontium. Saliva samples were collected, and clinical periodontal measurements were repeated at 2, 4, and 8 weeks after initial periodontal therapy in patients with CP. An enzyme-linked immunosorbent assay was used to investigate 8-OHdG levels of saliva samples. RESULTS: Statistically significant higher 8-OHdG levels of saliva and a significant decrease after initial periodontal therapy were determined in the CP group (p < 0.001). A significant positive correlation was found between 8-OHdG levels of saliva and clinical periodontal measurements (p < 0.001). CONCLUSION: Within the limits of this short-term preliminary study it can be concluded that the estimation of 8-OHdG levels in saliva may be used to evaluate the oxidative stress in periodontitis patients. It also appears that oxidative stress, which is reflected by salivary 8-OHdG levels, might reflect the present status of periodontal health.

Expression and significance of 8-OHdG in primary pterygium / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To detect oxidative DNA damage marker 8-hydroxy-2-deoxyguanosine(8-OHdG)in primary pterygium and normal conjunctival tissues, explore the role of oxidative DNA damage in the pathogenesis of pterygium. <p>METHODS: Totally 35 primary pterygium specimens were collected during surgery and 5 normal conjunctival specimens which above the normal temporal bulbar conjunctiva were collected. The expressions of 8-OHdG in pterygium tissues were detected by immunohistochemical method and compared with the normal conjunctival tissues. The difference of 8-OHdG expression between the two groups was compared. <p>RESULTS: There were 24(69%)pterygium specimens positive for 8-OHdG staining, limited to the nuclei of the epithelial layer. No substantial staining was visible in the subepithelial fibrovascular layers. All normal controls were negative for 8-OHdG staining. The difference of 8-OHdG expression between the two groups was statistically significant(<i>P</i>=0.007). <p>CONCLUSION: The increased levels of 8-OHdG in the pterygium tissues indicate that oxidative DNA damage maybe play an important role in the pathogenesis of pterygium.

Changes and Significance of Serum 8-hydroxy-2'-deoxyguanosine in Kawasaki Disease Children with Coronary Artery Lesions / 医学研究杂志

Objective To investigate the changes of serum 8-hydroxy-2'-deoxyguanosine(8-OHDG) in Kawasaki disease (KD) children and to explore the importance of 8-OHDG in predicting the severity of coronary artery lesions in Kawasaki Disease.Methods The serum 8-OHDG was measured in KD patients group (n =60),fever patients group (n =12) and health control group (n =12) by ELISA method.Among the KD patients,30 KD patients were in acute stage (10 cases had coronary artery lesions,20 coronary were normal) and 30 patients were in recovery stage.The serum 8-OHDG and brain natriuretic peptide (BNP) were also compared between patients with coronary artery lesions (CALs) and patients with no coronary artery lesions NCALs).ROC curve analysis was used to test the 8-OHDG and BNP predictive values in KD with coronary artery lesions.Results The serum level of 8-OHDG was higher in acute KD patients than recovery KD patients,fever patients and healthy children (P ＜ 0.05) The serum 8-OHDG was higer in CALs patients than the NCALs patients (P ＜ 0.05).The serum BNP was higer in CALs patients than the NCALs patients (P ＜ 0.01).Analysis of the ROC curve showed that serum 8-OHDG had a positive predictive value of 64.3％ and a negative predictive value of 93.8％for distinguishing KD with CALs from KD NCALs when cutoff value was 57.02pg/ml.The area under the curve was 0.820.The serum BNP had a a positive predictive value of 47.6％ and a negative predictive value of 100％ for distinguishing KD with CALs from KD NCALs when cutoff value was 815pg/ml.The area under the curve was 0.745.Conclusion The serum 8-OHDG may have better predictive value than BNP in diagnose KD children with coronary artery lesions.

The significance of 8-hydroxy-deoxyguanosine acid in the diagnosis of nonalcoholic steatohepatitis / 中华内科杂志

Objective To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid ( 8-OHdG) in the diagnosis of nonalcoholic steatohepatitis ( NASH).Methods Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People ′s Hospital of Tianjin from May 2013 to December 2015.A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study , including 20 nonalcoholic simple fatty liver ( NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy.The other 32 healthy subjects were studied as controls.Serum 8-OHdG, ALT, AST and GGT were tested.Nonalcoholic fatty liver disease activity score ( NAS ) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients.The correlations between serum 8-OHdG and serum ALT , AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated.In addition , the receiver operating characteristic ( ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients , and the cut-off value was determined.Results Serum 8-OHdG values in healthy controls , NAFL and NASH patients were (0.19 ±0.16) μg/L, (0.22 ±0.16) μg/L, (0.42 ±0.21) μg/L respectively.The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6.AUC of 8-OHdG was 0.901 with cut-off value 0.39 μg/L.Its sensitivity was 88.3%and specificity was 81.5%, which were higher than those of ALT.Conclusion The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.

The antifibrotic and fibrolytic properties of date fruit extract via modulation of genotoxicity, tissue-inhibitor of metalloproteinases and nuclear factor- kappa B pathway in a rat model of hepatotoxicity.

BACKGROUND: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-κB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases -1 and -2. METHODS: Rats were divided into the following groups: normal control, model control (CCl4 only), CCl4 + DFE, CCl4 + DPE and CCl4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl4 (0.4 ml/kg) 3× a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test. RESULTS: Both DFE and DPE significantly attenuated CCl4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-κB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases -1 and -2 suggesting their fibrolytic activity. CONCLUSION: Our data suggest that DFE or DPE can prevent liver fibrosis by suppressing genotoxicity and nuclear factor-κB inflammatory pathway and by promoting collagen degradation.

Short-term markers of DNA damage among roofers who work with hot asphalt.

BACKGROUND: Roofers are at increased risk for various malignancies and their occupational exposures to polycyclic aromatic hydrocarbons (PAHs) have been considered as important risk factors. The overall goal of this project was to investigate the usefulness of phosphorylated histone H2AX (γH2AX) as a short-term biomarker of DNA damage among roofers. METHODS: Blood, urine, and dermal wipe samples were collected from 20 roofers who work with hot asphalt before and after 6 h of work on Monday and Thursday of the same week (4 sampling periods). Particle-bound and gas-phase PAHs were collected using personal monitors during work hours. γH2AX was quantified in peripheral lymphocytes using flow cytometry and 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed in urine using ELISA. General linear mixed models were used to evaluate associations between DNA damage and possible predictors (such as sampling period, exposure levels, work- and life-style factors). Differences in mean biomarker and DNA damage levels were tested via ANOVA contrasts. RESULTS: Exposure measurements did not show an association with any of the urinary biomarkers or the measures of DNA damage. Naphthalene was the most abundant PAH in gas-phase, while benzo(e)pyrene was the most abundant particle-bound PAH. Post-shift levels of γH2AX and 8-OHdG were higher on both study days, when compared to pre-shift levels. Cigarette smoking was a predictor of γH2AX and urinary creatinine was a predictor of urinary 8-OHdG. Between-subject variance to total variance ratio was 35.3 % for γH2ax and 4.8 % for 8-OHdG. CONCLUSION: γH2AX is a promising biomarker of DNA damage in occupational epidemiology studies. It has a lower within-subject variation than urinary 8-OHdG and can easily be detected in large scale groups. Future studies that explore the kinetics of H2AX phosphorylation in relation to chemical exposures may reveal the transient and persistent nature of this sensitive biomarker of early DNA damage.