8-Hydroxy-2'-Deoxyguanosine (8-OH-2dG) as a Biomarker of Oxidative Stress (OS) in the Acute Exacerbation of Spontaneous Preterm Birth (SPTB)

Spontaneous preterm birth (SPTB) is characterized by the delivery of a baby before 37 completed weeks of gestation, and this condition is associated with significant health challenges for the newborn. Emerging evidence highlights the importance of biomarkers for understanding the mechanisms underlying SPTB. One such biomarker, 8-OH-2dG, plays a critical role in evaluating oxidative stress and its impact on pregnancy outcomes. It has been demonstrated that 8-OH-2dG is a product of oxidative DNA damage and is widely recognized as a key indicator of cellular oxidative stress. Elevated reactive oxygen species in SPTB result in higher levels of the DNA degradation product 8-OH-2dG in amniotic fluid, causing damage to maternal and fetal tissues that could lead to premature rupture of fetal membranes. Therefore, evaluating the role of 8-OH-2dG in SPTB is of great interest. This review provides an overview of the current knowledge on 8-OH-2dG as a biomarker for SPTB and aims to elucidate its mechanism in this condition.

Determination of urinary 8-hydroxy-2′-deoxyguanosine by capillary electrophoresis with molecularly imprinted monolith in-tube solid phase microextraction

Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been synthesized,and that was used as medium of in-tube solid phase microextraction(SPME).Coupled with capillary electrophoresis-electrochemical detection(CE-ECD),the system of extraction and detection of 8-OHdG in urinary sample had been developed.Because of its greater phase ratio combined with conv...

Expression of 8-hydroxy-2'-deoxyguanosine in gastric carcinomas

Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） was examined in 30 patients with gastric carcinomas. Methods： The expression of 8-OHdG and apoptosis in the gastric carcinoma were measured using the methods of immunocytochemistry and deoxynucleartididyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）, respectively. Results： Of the 30 cases, 25（83%） showed stronger immunoreactivity than normal control. The patients with poorly differentiated gastric carcinoma had a larger tumor size and higher labeling indices of TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated gastric carcinoma. Conclusion： Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic gastric injuries and determination of 8-OHdG is useful in assessing high-grade malignancy in gastric carcinomas.

Correlation between sperm DNA 8-Hydroxy-2'-deoxyguanosine level and semen quality

8-hydroxy-2’-deoxyguanosine (8-OHdG), a typical form ofDNA adducts, is a key molecular biomarker for DNA oxidativedamage. The aim of the present study was to evaluote the correla-tion between the sperm DNA 8-OHdG level and the semen quality.In 52 male infertile patients, the sperm DNA 8-OHdG level wasdetermined by a high performance liquid chromatograph with elec-trochemical detector and the semen quality was examined according

Effects of Explicit and Implicit Solvent Models on the Hydrolysis Cleavage of N-Glycosidic Bond in 8-Oxo-7,8-dihydro-2'-deoxyguanosine

8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit and implicit solvent molecules on the hydrolysis cleavage of N-Glycosidic bond in 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxo-dG） have been systematically clarified in the present work based upon two types of computational models. Detailed potential energy surface （PES） scans and full unconstraint optimizations for all the representative points on PESs were carried out at the B3LYP/6-31＋G（d） level of theory. The effect of implicit solvent was tested by single-point calculation at the SCRF/IEF-PCM model. The results illustrate that the direct hydrolysis model involving one explicit water molecule can’t provide a complete depiction of the hydrolysis process of 8-oxo-dG, attributed to the insufficiency of nucleophile activation and leaving group stabilization. The expansion hydrolysis model involving four explicit water molecules, however, facilitates discrete proton transfer and therefore produces smooth reaction surfaces for both the dissociative （SN1） and concerted （SN2） pathways. The presence of the implicit solvent substantially lowers all activation energies and the SN1 process is more favorable than the SN2 process. The data and insights present here agree well with the experimental results and have given out a baseline for the enzymatic deglycosylation reaction of 8-oxo-dG.

乌芪通络胶囊对糖尿病实验性大鼠ERK1/2蛋白及8-OHdG含量的影响

目的:观察乌芪通络胶囊对糖尿病实验性大鼠背根神经节ERK1/2蛋白及8-OHdG含量的影响,初步探讨乌芪通络胶囊治疗糖尿病周围神经病变的机制。方法:雄性SD大鼠80只,造模前随机选择14只为正常对照组,造模组66只。后者经腹腔注射链尿佐菌素(STZ),3天后将血糖值大于及等于16.7mmol/L的大鼠继续正常饲养10周后检测,将神经传导变慢、轴突萎缩、结周脱髓鞘的大鼠归入糖尿病周围神经病变(DPN)模型组,得到51只大鼠模型,将造模成功动物随机分为3组,即模型组、弥可保组、乌芪通络胶囊组,给药8周后进行取材,取相关背根神经节,采用Western杂交测定法检测背根神经节组织中ERK1/2蛋白表达强度,用免疫组化法测定背根神经节组织中8-OHdG的含量,各组间进行比较。结果:模型组ERK1/2蛋白、8-OHdG较正常组显著升高(P<0.05),中药组和西药组ERK1/2蛋白含量及8-OHdG的含量较模型组显著减低(P<0.05)。结论:乌芪通络胶囊可以使模型大鼠背根神经节中ERK1/2蛋白表达下调,使背根神经节中8-OHdG的含量减少,这可能是该药重要作用机制之一。

太阳光及紫外线照射诱发M13mp2噬菌体DNA产生8-OHdG的作用

[目的 ]分析太阳光及长波紫外线 (UVA)、中波紫外线 (UVB)诱发Ml3mp2噬菌体DNA产生 8 羟基脱氧鸟苷(8 OHdG)的作用。 [方法 ]用太阳光、UVA和UVB照射处理M13mp2噬菌体样品 ,以HPLC EC检测DNA样品中的 8 OHdG。 [结果 ] 1、3、5h太阳光照射和 2 8、10 8、2 5 0、5 0 0kJ/m2 剂量UVA照射后的样品均可检测到 8 OHdG含量增加 ,并存在与照射剂量的依存关系。较高剂量 (2 6kJ/m2 )UVB照射也可引起 8 OHdG的产生。 [结论 ]太阳光照射致M13mp2噬菌体突变作用中 ,存在DNA的氧化损伤 ,主要是UVA的作用。

An efficient synthesis of 2,2′-arylmethylene bis-(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) and 1,8-dioxooctahydroxanthenes using ZnO and ZnO-acetyl chloride

2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl chloride catalysts the reaction is limited to give only 1,8-dioxo-octahydroxanthenes 3a-k in very good yields.

8-hydroxy-2-(di-n-propylamino)tetralin intervenes with neural cell apoptosis following diffuse axonal injury

Previous studies have reported a neuroprotective effect of 8-hydroxy-2-（di-n-propylamino）tetralin （8-OH-DPAT） against traumatic brain injury. In accordance with the Marmarou method, rat models of diffuse axonal injury were established. 8-OH-DPAT was intraperitoneally injected into model rats. 8-OH-DPAT treated rats maintained at constant temperature served as normal temperature controls TUNEL results revealed that neural cell swelling, brain tissue necrosis and cell apoptosis occurred around the injured tissue. Moreover, the number of Bax-, Bcl-2- and caspase-3-positive cells increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. However, brain injury was attenuated, the number of apoptotic cells reduced, Bax and caspase-3 expression decreased, and Bcl-2 expression increased at 6, 12, 24, 72 and 168 hours after diffuse axonal injury in normal temperature control and in 8-OH-DPAT-intervention rats. The difference was most significant at 24 hours. All indices in 8-OH-DPAT-intervention rats were better than those in the constant temperature group. These results suggest that 8-OH-DPAT inhibits Bax and caspase-3 expression, increases Bcl-2 expression, and reduces neural cell apoptosis, resulting in neuroprotection against diffuse axonal injury. This effect is associated with a decrease in brain temperature.

2型糖尿病患者血清8-羟基脱氧鸟苷酸水平与大血管病变的相关性

目的探讨2型糖尿病(T2DM)患者血清8-羟基脱氧鸟苷酸(8-OHdG)和颈动脉内膜中层厚度(IMT)的关系。方法将42例T2DM患者根据IMT的不同分成轻度组(IMT<1.0 mm,27例)和重度组(IMT≥1.0 mm或存在硬化斑块,15例),采用ELISA法测定其血清8-OHdG水平,并与健康体检者进行比较。结果两组T2DM患者的血清8-OHdG水平均明显高于正常对照组,重度组8-OHdG水平明显升高,血清8-OHdG水平与IMT呈正相关均有统计学意义(P<0.05)。结论T2DM患者血清8-OHdG水平的增高与颈动脉IMT的增厚有关,提示血清8-OHdG水平增高是T2DM患者合并早期动脉粥样硬化的危险因素之一。

The Activity of Serum 8-Iso-Prostaglandin F2α as Oxidative Stress Marker in Patients with Diabetes Mellitus Type 2 and Associated Dyslipidemic Hyperglycemia

Background: Oxidative stress has been closely linked to the incidence of diabetic complications. Therefore, the aim of this research article was to study hyperglycemia and abnormal lipid profile in diabetic patient type 2 and its correlation with oxidative stress development as measured by 8-iso-PGF2α and 8-OHdG. Methods: Fifty (50) patients confirmed type 2 diabetes mellitus and eighty (80) non-diabetic control individuals were included in this study. All individuals were tested for blood glucose, lipid profile, 8-iso-PGF2α and 8-OHdG HdG. Results: The age of diabetic patients was observed to be ≥40 yrs in 96% and diabetes was frequently detected in female than in male patients (76% vs. 24%, p ere elevated in diabetic patients compared with control individuals (p < 0.0001) except in HDL-C, a significant decrease was recorded (p = 0.04). Serum 8-iso-PGF2α and 8-OHdG were elevated significantly in diabetic patients compared with non-diabetic control and a significant correlation was recorded between them (r = 0.6, p α was associated with Age (r = 0.394, p < 0.0001), FBG (0.553, p < 0.0001), LDL-C (r = 0.2, p = 0.023), TG (r = 0.176, p = 0.045) and TC (r = 0.2, p = 0.02). Also, 8-OHdG was associated with age (r = 0.558, p < 0.0001), FBG (r = 0.67, p < 0.0001), LDL-C (r = 0.28, p = 0.001), TG (r = 0.358, p < 0.0001) and TC (r = 0.33, p < 0.0001). Age, FBG, HbA1c, LDL-C, TG and TC showed a significant linear regression with 8-iso-PGF2α and 8-OHdG recording its role as significant predictors for the elevation of 8-iso-PGF2α and 8-OHdG. Therefore, hyperglycemia with oxidative stress development may play a role for dyslipidemia and diabetic complications. Conclusion: Diabetic patient’s type 2 has a higher rate of abnormal serum lipids and correlates significantly with lipid peroxidation and oxidized DNA bases as measured by 8-iso-PGF2α and 8-OHdG. Therefore, 8-iso-PGF2α and 8-OHdG could be used as oxidative biomarkers for evaluating diabetic patients with early prediction of its complications and cancer development.

Fabrication of the DNA/poly(3-methylthiophene) composite film modified electrode and its application for the study on the voltammetric behavior and determination of 8-hydroxy-2'-deoxyguanosine

A composite film of DNA/poly(3-methylthiophene)(P3MT) modified glassy carbon electrode(GCE) has been fabricated by electro-deposition method.P3MT film was first electropolymerized at the GCE and the DNA layer was then immobilized on the P3MT layer by electrochemical method.The voltammetric behavior of 8-hydroxy-2'-deoxyguanosine(8-OH-dG) at the composite film modified electrode was studied.The effects of scan rates,pH and the interference of uric acid(UA) on the voltammetric behavior and detection of 8-OH-dG were also discussed.The experimental results suggest that the electrochemical behavior of 8-OH-dG at the composite film modified electrode was greatly improved due to the combination of the advantages of P3MT and DNA.In 0.1 M pH 7.0 phosphate buffer solution(PBS),the anodic peak currents of 8-OH-dG were linear with the 8-OH-dG concentration in two intervals,viz.0.28―4.2 μM and 4.2―19.6 μM.The detection limit of 56 nM 8-OH-dG could be estimated(S/N=3).This proposed composite film modified electrode shows excellent reproducibility and stability.It may have the potential application for the detection of 8-OH-dG in human urine.

Elevated 8-oxo-7,8-dihydro-2'-deoxyguanosine in genome of T24 bladder cancer cells induced by halobenzoquinones

Halobenzoquinones（HBQs） are an emerging class of halogenated disinfection byproducts（DBPs） in drinking water, which raised public concerns due to potential carcinogenic effects to human bladder. Our previous work demonstrated that HBQs and hydrogen peroxide（H_2O_2）together generated oxidative DNA damage via a metal-independent and intercalationenhanced oxidation mechanism in vitro. This study further investigated the efficiency of various HBQs to induce oxidative DNA damage in T24 bladder cancer cells. Compared with T24 cells without treatment（3.1 lesions per 10~6 d G）, the level of 8-oxo-7,8-dihydro-2′-deoxyguanosine（8-oxod G） significantly increased by 1.4, 3.2, 8.8, and 9.2 times after treatment with tetrabromo-1,4-benzoquinone（TBBQ）, terachloro-1,4-benzoquinone（TCBQ）,2,6-dichloro-1,4-benzoquinone（2,6-DCBQ） and 2,5-dichloro-1,4-benzoquinone（2,5-DCBQ） for24 hr, respectively. Interestingly, we found that the oxidative potency of HBQs in T24 cells（2,5-DCBQ ≈ 2,6-DCBQ 〉 TCBQ 〉 TBBQ） is inconsistent with that of in vitro ds DNA oxidation（TCBQ 〉 TBBQ 〉 2,5-DCBQ 〉 2,6-DCBQ）, suggesting HBQs induce oxidative lesions in cellular genomic DNA probably involved with a complex mechanism.

2型糖尿病患者检测血清中IL-6和尿样中8-OHdG的变化

目的探讨白介素-6(IL-6)在2型糖尿病患者糖尿病发生、发展过程中的变化。了解健康人群尿样中8-羟基脱氧鸟苷(8-OHdG)含量的正常范围,探索尿样中8-OHdG含量水平能否作为反映2型糖尿病患者DNA氧化损伤程度的直接指标。方法用(酶联免疫吸附法)ELISA分析法检测40例2型糖尿病人及40例健康检查者IL-6水平;采用ELISA检测健康人和2型糖尿病患者尿样中8-OHdG的含量。结果 2型糖尿病患者血浆中IL-6明显高于正常对照组(P<0.01)。2型糖尿病患者尿样中的8-OHdG含量为(23.58±5.42)ng/mgCr,明显高于健康人的(14.54±5.10)ng/mg Cr(P<0.01)。结论 IL-6在糖尿病的发生、发展过程中发挥作用,观察其浓度变化对探讨糖尿病的发病机制、预防及指导用药均有重要价值;同时2型糖尿病患者的DNA氧化损伤水平均高于健康人群。

雌激素通过调节Nrf2/ROS信号通路诱导正常乳腺细胞生物学改变

目的探讨雌激素通过Nrf2/ROS信号通路对正常乳腺上皮细胞生物学改变的诱导作用。方法选取正常乳腺上皮细胞株MCF-10A和MCF-12A,实验设立空白组和雌激素组(5 nmol/L)。分别采用MTT法、LDH实验、酶联免疫吸附测定法(ELISA)、DCFH-DA荧光探针标记法和氧化酶活性测定、划痕实验、平板克隆实验、AnnexinV/PI双染色法检测干预后乳腺细胞的生物学表现;Western blot和PCR检测乳腺细胞中Nrf2、HO-1、NQO1蛋白及mRNA表达水平。结果雌激素可诱导细胞活力、迁移和克隆能力的增强,同时降低细胞凋亡水平。雌激素可以诱导ROS的积累,抑制细胞中SOD、GPX、CAT和TAC等氧化酶的活性,进而促进细胞中LDH和8-OHdG的水平升高,导致细胞毒性和DNA氧化损伤增加。此外,Western blot和RT-qPCR结果表明,雌激素诱导后可抑制Nrf2、HO-1和NQO1的表达。结论雌激素可以诱导正常乳腺细胞的增殖和降低细胞凋亡,并通过调节Nrf2/ROS信号通路来增加DNA的氧化损伤,进而诱导乳腺细胞的生物学改变。

The Effects of HBx Gene on the Expression of DNA Repair Enzymes hOGG1 and hMYHα mRNA in HepG2 Cells

To observe the alteration in the expression of DNA repair enzymes hOGG1 and hMYHa and the change in 8-OHdG levels in the HBx gene-transfected cells HepG2/HBx and to explore the mechanisms of the HBV-associated hepatocellular carcinoma, the gene-transfected cells HepG2/HBx which stably expressed HBx was established, and the effect of HBx on the cell cycle and proliferation of HepG2 was examined. By using the β-actin as the interior control, real-time polymerase chain reaction （Real-time qPCR） was employed to quantitatively detect the expression of DNA repair enzymes hOGG1 and hMYHα in the HepG2/HBx, the control cells HepG2 and HepG2 transfected with pcDNA3.1 vector （HepG2/pDNA3.1）. The 8-OHdG levels were determined by HPLC/ECD in the established gene-transfected cells HepG2/HBx and the control cells HepG2 and HepG2/pcDNA3.1. Our results showed that the expression of DNA repair enzyme hMYHα in the HepG2/HBx （0.021±0.007） was significantly lower than that of HepG2 （0.099±0.041） （P〈0.05） and HepG2/pDNA3.1 （0.121±0.005） （P〈0.05）. However, the no significant differences existed in the expression of DNA repair enzyme hOGG1 among the three cell strains （P〉0.05）. The 8-OHdG level in the HepG2/HBx was significantly higher than that in HepG2 and HepG2/pcDNA3.1 （P〈0.05）. It is concluded that HBx gene may inhibit the expression of DNA repair enzyme hMYHα mRNA to impair the ability to repair the intracellular DNA oxidative damage, to increase the oxidative DNA-adduct 8-OHdG and to affect the nucleotide excision repair function, thus participate in the occurrence and development of hepatocellular carcinoma.

4,4’-Methylenebis(2-chloroaniline) (MBOCA) May Be Highly Toxic and a Carcinogen Based on an Experimental Study with Mice

4,4’-Methylenebis(2-chloroaniline) (MBOCA) is a probable human carcinogen. Few studies have been performed regarding the genotoxicity of MBCOA, and the MBOCA metabolic pathway is not fully understood. We treated four-week-old ICR male mice weighing 25 - 30 g with MBOCA and observed the effects of MBOCA on the internal organs. It can be concluded that MBOCA is a carcinogen and also affects gene regulation. Oral or topical administration of 50 mg/kg, 100 mg/kg or 200 mg/kg MBOCA resulted in 56% - 81% of mice showing unusual inflammation, degeneration, and dysplasia in kidney, liver, stomach, intestine and urinary bladder based on histology. Furthermore, we investigated the association between oxidative DNA damage and MBOCA exposure by measuring plasma level of 8-hydroxydeoxyguanosine (8-OHdG). The results showed that the MBOCA-treated mice had significantly higher 8-OHdG levels than the control mice. This study confirms that MBOCA is potentially carcinogenic and highly toxic to both animals and humans.

2型糖尿病人群DNA氧化损伤情况分析

目的：了解2型糖尿病人群DNA氧化损伤的情况。方法：采用酶联免疫吸附法（ELISA）检测，健康人群和2型糖尿病人群尿样DNA中8-OHdG的含量。结果：尿样DNA中的8-OHdG水平显示，高于半年病程2型糖尿病病例和2型糖尿病伴肾病病例分别为（22．37±5．62）ng／mgGr和（23．80±7．58）ng／mgGr，明显高于健康人的（15．74±6．10）ng／mgGr（P〈0．05）。结论：高于半年病程2型糖尿病病例和2型糖尿病伴肾病病例的DNA氧化损伤水平均高于健康人群。对于预防和监测2型糖尿病病人，测定尿样中8-OHdG含量是一个简单、准确的方法。

8-羟基脱氧鸟苷酸和血管内皮生长因子与糖尿病肾病的关系

目的探讨DNA氧化损伤标志物血清8-羟基脱氧鸟苷酸(8-OHdG)和血管内皮生长因子(VEGF)与糖尿病肾病(DN)的关系。方法随机检测71例DN患者,73例糖尿病患者及健康对照者47名,采用酶联免疫吸附实验(ELISA)法测定其血清8-OHdG、VEGF水平24h微量白蛋白,并与47名健康对照者进行比较。结果 8-OHdG和VEGF水平DN组显著高于糖尿病组(P<0.01),糖尿病组高于正常对照组(P<0.05)。大量蛋白尿组明显高于微量蛋白尿组(P<0.05)。HbA1c>10%组明显高于糖化血红蛋白<9%组(P<0.05)。结论 DN与血清8-OHdG、VEGF有关,氧化应激和VEGF参与DN发生发展过程。

五子衍宗方对环磷酰胺致小鼠睾丸细胞DNA损伤的影响

目的探讨五子衍宗方(枸杞子、菟丝子、覆盆子、车前子、五味子)对环磷酰胺致成年雄性小鼠睾丸细胞DNA损伤的影响。方法将50只成年雄性Balb/C小鼠中40只腹腔注射环磷酰胺后随机均分为模型对照组(生理盐水)以及五子衍宗方低、中、高剂量组(100、200、400 mg/kg),10只另设正常对照组(生理盐水),乙醚麻醉小鼠后颈椎脱臼处死。检测小鼠精子数量、精子活率及精子畸形率,酶联免疫吸附测定法(ELISA)法检测血清中8-羟基脱氧鸟苷(8-OHdG)的含有量,单细胞凝胶电泳技术检测睾丸细胞DNA损伤程度,Western blot检测睾丸组织中磷酸化的肿瘤抑制蛋白53(p-P53)、γ位磷酸化的组蛋白(γ-H2AX)蛋白表达。结果相较于模型对照组,五子衍宗方各组可显著升高小鼠精子数量、精子活率,显著降低精子畸形率、血清8-OHdG水平,显著降低睾丸组织中p-P53与γ-H2AX蛋白表达。结论五子衍宗方能通过下调p-P53、γ-H2AX蛋白表达来显著减轻环磷酰胺致小鼠睾丸细胞DNA损伤。