Mediating effect of oxidative stress on association between nicotine and unexplained recurrent spontaneous abortion / 环境与职业医学

Background Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion (URSA) through oxidative stress. Objective To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA. Methods Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHdG, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHdG and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model. Results The median concentrations (creatinine corrected) of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were 7.78, 4.84, and 44.10 μg·g−1, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g−1, respectively. The concentrations of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group (P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q1 groups of nicotine and 8-iso-PGF2α, the OR (95%CI) values of URSA in the Q4 groups were 4.20 (1.33-13.29) and 6.25 (1.66-23.59), respectively. Compared with the Q1 group of 8-OHdG, the OR (95%CI) values of URSA in the Q1, Q2, and Q3 groups were 5.47 (1.43-20.93), 4.24 (1.28-14.07), and 6.36 (1.82-22.28), respectively. The results of multiple linear regression showed that after adjusting confounding factors, there was a positive correlation between urinary nicotine and 8-OHdG in both the case group and the control group, and the b (95%CI) values were 0.76 (0.67-0.86) and 0.81 (0.67-0.95) respectively; there was a positive correlation between urinary nicotine and 8-iso-PGF2α in both the case group and the control group, and the b (95%CI) values were 0.65 (0.55-0.75) and 0.76 (0.64-0.87), respectively. The results of dichotomous mediating analysis showed that the mediating effect of 8-iso-PGF2α and its 95%CI on the relationship between nicotine exposure and URSA was 1.518 (0.749-2.311). Conclusion Internal nicotine exposure is a risk factor for URSA and is positively correlated with oxidative stress, and it may lead to URSA through lipid peroxidation damage.

Can serum 8-hydroxy-2'-deoxyguanosine levels reflect the severity of pulmonary arterial hypertension?

SUMMARY OBJECTIVE: Oxidative stress plays a pivotal role in the pathogenesis of pulmonary arterial hypertension. 8-Hydroxy-2'-deoxyguanosine is a sensitive biomarker that reflects the degree of oxidative damage to DNA. We investigated whether serum 8-Hydroxy-2'-deoxyguanosine is a clinically useful biomarker for the severity of pulmonary arterial hypertension. METHODS: We measured serum 8-Hydroxy-2'-deoxyguanosine levels in 25 patients (age 37±13 years, 68% women) diagnosed with idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease. The severity of pulmonary arterial hypertension was evaluated by six-min walking distance, World Health Organization functional class, and serum brain natriuretic peptide levels. Age and gender-matched 22 healthy subjects served as the control group. RESULTS: The comparison of 8-Hydroxy-2'-deoxyguanosine levels between patients and controls was not statistically different [(19.86±9.79) versus (18.80±3.94) ng/mL, p=0.622)]. However, there was a significant negative correlation between 8-Hydroxy-2'-deoxyguanosine levels and six-min walking distance (r= −0.614, p=0.001). Additionally, serum 8-Hydroxy-2'-deoxyguanosine levels in patients with functional class III-IV were significantly higher than those with functional class I-II (functional class III-IV 32.31±10.63 ng/mL versus functional class I-II 16.74±6.81 ng/mL, respectively, p=0.003). CONCLUSION: The 8-Hydroxy-2'-deoxyguanosine levels were significantly correlated with exercise capacity (six-min walking distance) and symptomatic status (functional class), both of which show the severity of pulmonary arterial hypertension in patients.

Effect of 8-hydroxy-2-(Di-n-propylamino)tetralin on hypoxia inducible factor 1 alpha expression following diffuse axonal injury in rats / 中国组织工程研究

BACKGROUND: 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) can decrease brain temperature, which is the potential mechanism of its neuroprotection. OBJECTIVE; To investigate the effect of 8-OH-DPAT on hypoxia inducible factor 1 a in the brain tissue of rats with diffuse axonal injury, and to explore the underlying mechanism of 8-OH-DPAT exerting neuroprotection in rats of diffuse axonal injury. METHODS; The study was approved by the Laboratory Animal Ethical Committee of General Hospital of Northern Theater Command. Wistar rats were randomly assigned into four groups: Model group (n=35), constant temperature group (n=35), 8-OH-DPAT group (n-35) and normal group (n=7). Excepting the normal group, rat models of diffuse axonal injury were established according to Marmarou method. Rat models in the constant temperature and 8-OH-DPAT were intraperitoneally injected with 8-OH-DPAT, but those in the model and normal groups were intraperitoneally injected with physiological saline. The body temperature of rats in the constant temperature group was maintained at (37.0±0.5)°C using the blanket. The body temperature of rats was measured every 1 hour. Then, brain injury and hypoxia inducible factor 1a expression level were observed at 6, 12, 24, 72, and 168 hours after diffuse axonal injury in rats. RESULTS AND CONCLUSION: (1) Compared with the constant temperature and model groups, brain temperature was significantly lower in the 8-OH-DPAT group at 1 hour following modeling (P < 0.05), became lowest at 2 hours (P < 0.05), and then gradually increased. (2) Hematoxylin-eosin staining results revealed that brain injury was more serious in the model group, followed by constant temperature group, and lightest in the 8-OH-DPAT group. (3) Results of immunohistochemistry and ELISA showed that the expression level of hypoxia inducible factor 1a in the serum and brain tissue was lowest in the normal group. In the 8-OH-DPAT group, the expression level of hypoxia inducible factor 1a was increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. Compared with the model group, the expression level of hypoxia inducible factor 1a in serum and brain tissue in the constant temperature and 8-OH-DPAT groups was significantly decreased (P < 0.05 or P < 0.01), especially the 8-OH-DPAT group (P < 0.01). (4) These results imply that 8-OH-DPAT decreases hypoxia inducible factor 1a expression in brain tissue of diffuse axonal injury rats by reducing brain temperature, alleviates the degree of nerve injury, and exerts a neuroprotective effect.

The effectiveness of eugenol against cisplatin-induced ototoxicity / A eficácia do eugenol contra a ototoxicidade induzida pela cisplatina

Abstract Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.

Resumo Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes.

Effect of diesel exhaust exposure on 8-hydroxy-2' deoxyguanosine level in biological samples of automobile manufacturing workers / 中国职业医学

OBJECTIVE: To investigate the feasibility of using 8-hydroxy-2'deoxyguanosine(8-OHdG) in blood and urine samples as biomarkers for the evaluation of human DNA oxidative damage caused by diesel exhaust(DE). METHODS: A convenient sampling method was used to select 56 male workers exposed to DE in a car manufacturing factory as exposure group, and 52 male workers without exposure to DE were selected as the control group.Urine samples and blood samples were collected from workers in the 2 groups 8 hours after work, and the levels of 8-OHdG in urine and plasma were measured by ultra-high performance liquid chromatography tandem mass spectrometer. RESULTS: The median level of urinary 8-OHdG in the exposure group was higher than that of control group(2.54 vs 2.03 μg/g Cr, P<0.05). The median levels of plasma 8-OHdG in the exposure group and control group showed no statistical significance(32.20 vs 31.40 ng/L, P>0.05). CONCLUSION: The urinary 8-OHdG can be used as a biomarker for evaluating the oxidative damage induced by DE exposure.

One new 2-(2-phenylethyl) chromone derivative from agarwood of Aquilaria crassna in Cambodia / 中草药

Objective: To study the chemical constituents of agarwood originating from Aquilaria crassna in Cambodia. Methods: The compounds were isolated and purified by silica gel column chromatography and semi-preparetive HPLC and so on. Their structures were identified by spectroscopic data. All compounds were tested for cytotoxic activities against two human cancer cell lines by MTT method. Results: Four compounds were isolated and elucidated as 6-methoxy-8-hydroxy-2-(2-phenylethyl) chromone (1), 6-methoxy-7-hydroxy-2-[2-(4-methoxyphenyl) ethyl] chromone (2), 7β,8β-epoxy-6α-hydroxy-5α-methoxy-5,6,7,8-tetrahydro-2-[2-(4- methoxyphenyl) ethyl] chromone (3), and rel-(1aR,2R,3R,7bS)-5,6-epoxy-7,8-dihydroxy-5,6,7,8-tetrahydro-2-[2-(4-methoxyphenyl) ethyl] chromone (4). Conclusion: Compound 1 is a new compound, while compounds 2-4 are isolated from this agarwood for the first time. Among them, compound 4 showed inhibitory activities against SGC-7901 and A549 cells.

Serum 8-hydroxy-2-deoxyguanosine level of radiation workers in hospitals / 中华放射医学与防护杂志

Objective To explore the influence of long-term low-dose ionizing radiation on 8-hydroxy-2-deoxyguanosine(8-OHdG) level in the serum of radiation workers in hospitals.Methods 307 age-and sex-matched hospital radiation workers were recruited by stratified random sampling method.After deleting the subjects without dosage information,230 individuals were divided into four groups according to their job title [including diagnostic radiology (n =75),radiotherapy (n =60),nuclear medicine (n =41) and interventional radiology (n =54)].Serum 8-OHdG level was measured by ELISA assay.Results According to the statistical analysis,there was significant difference in the serum 8-OHdG level among four groups (F =9.071,P ＜ 0.05),and the content of serum 8-OHdG was significantly higher in the interventional radiology group than that in the groups of diagnostic radiology,radiotherapy and nuclear medicine (t =-4.473,-3.011,-2.189,P ＜ 0.05).There were significant differences in serum 8-OHdG level among different dose groups and working period groups(F =7.659,3.058,P ＜ 0.05).The serum 8-OHdG levels significantly increased along with exposure dose and working period (r =0.300,0.142,P ＜ 0.05).Conclusions Serum 8-OHdG may be a potential biomarker of oxidative DNA damage in radiation workers exposed to low-dose ionizing radiation.

Effect of DNA single strand breaks and 8-OHd G production on cadmium-induced toxicity on human embryonic kidney epithelial cells / 中国职业医学

OBJECTIVE: To explore the effects of cadmium chloride( CdCl_2) on DNA single strand breaks and the production of 8-hydroxy-2'-deoxyguanosine( 8-OHdG) in human embryonic kidney epithelial cells( HEK cells). METHODS: HEK cells in logarithm growth phase were divided into 5 groups and incubated with the different concentrations of CdCl_2( 0. 0,2. 5,5. 0,10. 0 and 20. 0 μmol/L) for 24,48 and 72 hours in vitro. After harvesting the cells,DNA single strand breaks was tested by single cell gel electrophoresis,and the level of 8-OHdG was measured using the enzyme linked immunosorbent assay. RESULTS: The Olive tail moment was statistically significant in the main effect of CdCl_2 exposed HEK cells( P < 0. 01). Among them,when HEK cells were exposed to 5. 0 μmol / L of CdCl_2,the Olive tail moment began to have a statistical significant increasing trend compared with the 0. 0 μmol / L group( P < 0. 05); when CdCl_2 concentration was 2. 5-10. 0 μmol / L,the Olive tail moment lengthened with the increasing dose of cadmium exposure,showing a doseeffect relationship( P < 0. 05). The tail DNA% was statistically significant in the interaction between exposure treatment and exposure time in HEK cells( P < 0. 01). Among them,when CdCl_2 concentration was at 2. 5-10. 0 μmol / L at 24 hours time point and 5. 0-20. 0 μmol / L at 48 hours time point,the tail DNA% raised with the increasing dose of cadmium exposure,showing a dose-effect relationship( P < 0. 05). The tail DNA% at 3 time points of 24,48 and 72 hours after exposure to 20. 0 μmol / L of CdCl_2 in HEK cells increased with the increasing time of cadmium exposure,showing a timeeffect relationship( P < 0. 05). The level of 8-OHdG had statistical significance in the main effect of CdCl_2 exposure treatment in HEK cells( P < 0. 05). Among them,the level of 8-OHdG was first significantly increased only after exposure to 10. 0 μmol / L CdCl_2 compared with the 0. 0 μmol / L group( P < 0. 05). After treatment with Ca Cl2,there was no doseeffect relationship and time-effect relationship found between the cadmium chloride exposure and tail length as well as the tail / head length ratio and 8-OHdG level. CONCLUSION: To a certain extent,CdCl_2 exposure may cause both DNA single strand breaks and 8-OHdG production in HEK cells. Compared with 8-OHdG,the DNA single strand breaks show more significant change with a lower dose of cadmium treatment,which may be related to its higher sensitivity to cadmium toxicity than 8-OHdG.

Urinary 8‑hydroxydeoxyguanosine as a marker of oxidative stress induced genetic toxicity in oral cancer patients.

Context: Recently, non‑communicable diseases have snatched the lead from infectious diseases in causing mortality. Of these, oral cancer accounts for a significant proportion of deaths. Every year in India significant percentage of newly diagnosed malignancy is oral cancer attributed to various reasons. Aims: The aim of this study was to assess the extent of oxidative stress and its effect on modification of DNA by urinary nucleoside 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels in oral cancer subjects. To see the relationship between the nucleoside 8‑OHdG and antioxidant capacity ferric reducing ability plasma (FRAP) in oral cancer subjects. Settings and Design: Case–control study included three groups with 60 volunteers, who were divided into 30 controls, and equal number of clinically diagnosed oral cancer male patients: (Subdivided into newly diagnosed [n = 15] and 1‑year treatment follow‑up oral cancer subjects [n = 15]). Materials and Methods: A random urine sample was used for analysis of 8‑OHdG concentration. Serum triglycerides, lipid peroxidation, protein thiols, and FRAP assay were performed by spectrophotometric technique. Statistical Analysis Used: Student’s t‑test and one‑way analysis of variance were performed for group comparison and Pearson’s correlation analysis were used. A P < 0.05 was considered the optimum level of significance. Results: The urinary 8‑OHdG and serum malondialdehyde levels were significantly elevated in newly diagnosed oral cancer subjects in their 1‑year treatment compared to the control group (P < 0.05). A significant correlation was observed between urinary 8‑OHdG and FRAP in both groups of oral cancer subjects. Conclusions: Urinary 8‑OHdG can be a useful diagnostic marker of oxidative DNA damage in oral cancer subjects.

Relationship between phospholipase C zeta immunoreactivity and DNA fragmentation and oxidation in human sperm

OBJECTIVE: The study aimed to evaluate the feasibility and reproducibility of measuring phospholipase C zeta (PLCzeta) using immunostaining in human sperm and to investigate the relationship between PLCzeta immunoreactivity and DNA fragmentation and oxidation in human sperm. METHODS: Semen samples were obtained from participants (n=44) and processed by the conventional swim-up method. Sperm concentration, motility, normal form by strict morphology, DNA fragmentation index assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling method and immunofluorescent expression for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and PLCzeta were assessed. RESULTS: When duplicate PLCzeta tests were performed on two sperm samples from each of the 44 participants, similar results were obtained (74.1+/-9.4% vs. 75.4+/-9.7%). Two measurements of PLCzeta were found to be highly correlated with each other (r=0.759, P<0.001). Immunoreactivity of PLCzeta was not associated with donor's age, sperm concentration, motility, and the percentage of normal form as well as DNA fragmentation index. However, immunoreactivity of PLCzeta showed a significant negative relationship with 8-OHdG immunoreactivity (r=-0.404, P=0.009). CONCLUSION: Measurement of PLCzeta by immunostaining is feasible and reproducible. Lower expression of PLCzeta in human sperm may be associated with higher sperm DNA oxidation status.

Relationship Between Mitochondrial DNA Related Factors and Traditional Chinese Medical Syndrome Types in Primary Osteoporosis Patients / 广州中医药大学学报

Objective To investigate the biological characteristics of primary osteoporosis syndrome types from the perspective of mitochondrial DNA ( mtDNA) , thus to reveal the nature of osteoporosis and its traditional Chinese medical syndrome types. Methods A total of 210 osteoporosis women patients meeting the diagnostic criteria, inclusion criteria and exclusion criteria were collected from July of 2011 to October of 2013. The osteoporosis patients were differentiated into the syndrome types of yin deficiency of liver and kidney ( N=67) , yang deficiency of spleen and kidney ( N=70) and qi stagnation and blood stasis ( N=73) . And a total of 69 age-matched post-menopause non-osteoporosis patients were chosen as the control group, which were classified into the syndrome of harmony of Qi and blood. The peripheral blood was sampled for detecting mtDNA copy number with fluorescent quantitatitation PCR and for examining 8-hydroxy-2’-deoxyguanosine ( 8-OHdG) content by enzyme-linked immunosorbent assay (ELISA) . Statistical methods was used to analyze the correlation of bone mineral density (BMD) with mtDNA copy number and 8-OHdG content in different groups. Results The difference of mtDNA copy number was significant between the osteoporosis patients and non-osteoporosis patients (P<0.05), and was also significant among the three syndrome types of osteoporosis patients (P<0.05) . And 8-OHdG content showed the same features between the osteoporosis patients and non-osteoporosis patients (P<0.05) and among the three syndrome types of osteoporosis patients (P<0.05) . The correlation analysis results showed that mtDNA copy number was positively correlated with BMD, while 8-OHdG was negatively correlated with BMD in each group. Conclusion The mtDNA copy number and 8-OHdG content are correlated with the syndrome types of primary osteoporosis patients, and close correlation is shown between spleen-kidney yang deficiency and 8-OHdG, and between liver-kidney yin deficiency and mtDNA copy number.

Chemical Composition, Antioxidant Activities and Protective Effects of Sideritis italica Extract on C2C12 Oxidative Stress.

Aims: Sideritis italica is a medicinal plant used for medical purposes mainly based on experiences rather than scientific evidence. Biological properties, composition of primary and secondary metabolites as well as the antioxidant capacity were investigated on samples from wild plant. Methodology: The ultrastructure of aerial parts and quantitative distribution of pigments, including chlorophylls and amino acids, as well as the main class of secondary metabolites (phenols, flavonoids, flavonols and proanthocyanidins) were investigated. The extracts were tested by radical scavenging assays (DPPH, ABTS) and pharmacological assays (antiproliferative activity, effects on ROS production and protective effects against DNA damage induced by hydrogen peroxide) for their effects on C2C12 cell line. Results: Scanning electron microphotography confirms the presence of pharmacognostic characteristics, such as glandular and non-glandular trichomes on aerial parts. The chemical analysis indicates that the leaves are the most important part of the plant, and ethanol/water 70/30 is the preferable extraction solvent. The highest concentration of all metabolites was found in 70% ethanol extract of leaves. The antiradical assays and the in vitro tests on mouse myoblast cells C2C12 confirm the biological activities of the extract. C2C12 culture medium supplemented with extract, at doses (5-200μg/ml) not interfering with cell viability, was seen to modulate the ROS production and balance the increased oxidative stress induced by hydrogen peroxide. The treatment of C2C12 cells with 200 μg/ml of extract results in a percentage reduction of ROS of -60% and -71%, compared to untreated and H2O2 treated groups, respectively, P<.05. The quantitative reduction of 8- hydroxy-2’-deoxyguanosine (8-OH-dG), which is a biomarker of free radical DNA damage, confirms the protective effect of S. italica extract on oxidative stress at basal condition as well as in presence of exogenous stimuli (-11 and -7%, at 20μg/ml, respectively versus untreated and H2O2 groups, P<.05). Conclusion: The results obtained in the present study support the rational base for the medicinal use of plant and extracts in modulating the free radical metabolism and balancing the oxidative stress.

Ameliorating effect of tannic acid on high glucose or AGEs induced oxidative stress and micro-inflammatory state in glomerular mesangial cells / 吉林大学学报(医学版)

Objective To investigate the effect of tannic acid on glomerular mesangial cells (GMC),and to clarify the mechanism of tannic acid in improving the pathological changes of diabetic nephropathy (DN)from the aspect of oxidative stress and micro-inflammation. Methods The glomerular mesangial cells were treated with glucose (30 mmol·L-1 )or advanced glycosylation end-products (AGEs)bovine serum albumin(BSA)(250 mg·L-1 )and then different concentrations of tannic acid (10,20,40 and 80μmol·L-1 )were added into the GMC.The cells cultured by normal glucose or treated with BSA were used as control groups and then the level of malonic dialdehyde (MDA), glutathione peroxidase (GSH-Px ), superoxide Dismutase (SOD ), CAT (Catalase ) activities and 8-hydroxy-2′-deoxyguanosine(8-OHdG)levels in the culture supernatant 48 h after culture were determined by colorimetry and ELISA method. The expressions of intercellular cell adhesion molecule-1 (ICAM-1 ) protein, monocyte chemotactic protein 1 (MCP-1 ) and ICAM-1 mRNA in GMC were detected by immunohistochemical staining and RT-PCR method.Results Compared with high glucose and AGEs groups,the MDA levels in tannic acid groups were reduced significantly(P<0.05);the activities of GSH-Px,SOD and CAT were increased significantly(P<0.05 or P<0.01);the 8-OHdG levels in annic acid groups were significantly reduced (P<0.05). Compared with high glucose and AGEs groups,the expressions levels of ICAM-1 protein in 40 and 80μmol· L-1 tannic acid groups were decreased (P<0.05 ). The mRNA expressions levels of MCP-1 and ICAM-1 were significantly lower than those in high glucose group (P<0.01 ).Conclusion Tannic acid could protect GMC against the damage of oxidative and inflammatory mediators,thereby delaying and improving the glomerular lesions of DN.

Medical Effects of Balneology of Radioactive Hot Springs / 日本温泉気候物理医学会雑誌

  Many things are unknown about the radioactive hot springs. We have not yet obtained the conclusive evidence of whether the low dose of radiation by radon in the hot springs is healthful or harmful for us. Thus, to grasp the present conditions of the radioactive hot springs scientifically, I reviewed them from the many-sided viewpoints in the following order.  At first, some basic information on the radioactive hot springs was summarized to look around them all over. Next, based on the hot spring analysis tables obtained from three representative hot spring resorts in our country, the effective ingredients such as radon, metals, and several kinds of ions presented in the spring waters were evaluated for each hot spring.  Then, radon as an element, the radon exposure, and the active oxygen species generated by the radiation of radon were explained to understand the fundamental action of radon. Furthermore, some reports related to the lung cancer risk by inhaling radon were introduced to take the cancer risk in the radioactive hot springs into consideration.  Since the oxidative DNA damage induced by hydroxyl radical is considered to be a cause for cancers, it was discussed that the urinary concentrations of 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of the DNA damage, could be used as an index for evaluating the effects of the radioactive hot springs on human health.

Medical Effects of Balneology of Radioactive Hot Springs / 日本温泉気候物理医学会雑誌

  Many things are unknown about the radioactive hot springs. We have not yet obtained the conclusive evidence of whether the low dose of radiation by radon in the hot springs is healthful or harmful for us. Thus, to grasp the present conditions of the radioactive hot springs scientifically, I reviewed them from the many-sided viewpoints in the following order.  At first, some basic information on the radioactive hot springs was summarized to look around them all over. Next, based on the hot spring analysis tables obtained from three representative hot spring resorts in our country, the effective ingredients such as radon, metals, and several kinds of ions presented in the spring waters were evaluated for each hot spring.  Then, radon as an element, the radon exposure, and the active oxygen species generated by the radiation of radon were explained to understand the fundamental action of radon. Furthermore, some reports related to the lung cancer risk by inhaling radon were introduced to take the cancer risk in the radioactive hot springs into consideration.  Since the oxidative DNA damage induced by hydroxyl radical is considered to be a cause for cancers, it was discussed that the urinary concentrations of 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of the DNA damage, could be used as an index for evaluating the effects of the radioactive hot springs on human health.

Protective Effect of Fish Oil Supplementation on DNA Damage Induced by Cigarette Smoking.

The study examined the influence of fish oil (FO) supplementation on serum 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels as indicated by DNA damage markers and total antioxidant capacity (TAC) among male cigarette smokers. This double-blind, placebo-controlled randomized study was conducted among healthy cigarette smokers (n=40) who were part of a larger prospective cohort study. Twenty smokers were randomly selected to receive FO for 3 months (1 g/day), and another 20 smokers received a placebo for 3 months; 8-OHdG and TAC levels were measured in blood samples before and after the intervention. Serum 8-OHdG significantly decreased (p=0.001) and TAC increased (p<0.001) after 3 months of treatment with FO. Between baseline and endline, the difference in 8-OHdG significantly correlated with the difference in TAC among smokers who received FO (r=-0.540, p=0.014). The study provides evidence that FO supplementation can modify decreased antioxidants and increased oxidative DNA damage in cigarette smokers.

Oxidative Stress Markers in Children with Autism Spectrum Disorders.

Aims: The etiology of autism spectrum disorders (ASD) remains elusive, but oxidative stress has been suggested to play a pathological role. The understanding of the potential role of oxidative stress in the etiopathogenesis of autism would be very useful for earlier clinical, therapeutic or preventive strategies. Sample: To evaluate the redox status, we quantified the activity of the antioxidant enzyme catalase (CAT), glutathione concentration (GSH) and markers of damage to biomolecules, malonyldialdehyde (MDA) and 8–hydroxy-2deoxyguanosine (8OHdG) in peripheral blood samples. Place and Duration of Study: Sample: Department of Neuropediatrics and Technology Science Division. International Center for Neurological Restoration (CIREN), Havana, Cuba. May 2011- June 2012. Methodology: We included 45 children with autism (36 males and 9 females, age-range from 3 to 11 years). 42 children of the same age were selected as a control group. The diagnosis of autism was made based on the criteria of autistic disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) (American Psychiatric Association, 1994). Results: The total GSH content in autistic patients was significantly lower compared with the control group (0.24 ± 0.162 vs. 0.94 ± 0.115, respectively, p ≤ 0.001). Higher serum CAT, MDA and 8OHdG levels were found in children with autism compared with controls (CAT, 2.836 ± 0.479 vs. 0.689 ± 0.157, p ≤ 0.001; MDA 8.6 ± 0.5 vs. 1.76 ± 0.33 p ≤ 0.001, and 8OHdG 13.134 ± 1.33 vs.1.46 ± 0.326, p ≤ 0.001). Conclusion: The present study supports the notion that oxidative stress is associated with autism, but additional researches are needed to investigate how it may contribute to autistic pathophysiology and these studies are currently in progress.

Effects of oxidative damage of DNA on pathogenesis of pterygium / 中华实验眼科杂志

Background Pterygium is a relatively common eye disease,but its aetiology and pathogenesis remain uncertain.At present,the study on pterygia focuses on understanding its underlying mechanism.Objective This study was to detect the expression of 8-hydroxy-2'-deoxyguaine (8-OHdG),a marker of oxidative damage of DNA,and bcl-2,a gene related with apoptosis,on the pterygium tissue.Methods Thirty pterygium tissue specimens were obtained during the surgery with the primary pterygium 24 cases and recurrent pterygium 6 cases.In addition,20 normal conjunctival specimens from retinal detachment surgery and strabismus surgery were collected.The expressions of 8-OHdG and bcl-2 in pterygium tissue were detected using immunochemistry and compared with the normal conjunctival tissue.The difference in the expressions of 8-OHdG and bcl-2 among different specimens was compared by x2test,and the relationship between 8-OHdG expression and bcl-2 expression was evaluated by Kappa test.Results The positive expressing rate of 8-OHdG in the pterygium tissue was 62.5％ and 83.3％ in the primary and recrudescence pterygium tissue,respectively,but the expression of 8-OHdG was absent in the normal conjunctiva tissue.No significant difference was found in the positive expressing rate of 8-OHdG between primary and recrudescence pterygium tissue(x2 =0.938,P＞0.05).The bcl-2 expressing rate was 90.0％ and 87.5％ in the primary and recrudescence pterygium tissue,respectively.However,that in the normal conjunctival tissue was absent.No significant difference was seen in the bcl-2 expression rate between primary and recrudescence pterygium tissue (x2=0.833,P ＞ 0.05).Of the 27 pterygium tissue with bcl-2 positive expression,8-OHdG showed the positive expression in 20 specimens,and 3 specimens with the bcl-2 negative response were absent reactive to 8-OHdG,showing insignificant difference between them (P＞0.05).The relationship between 8-OHdG expression and bcl-2 expression was concord in a certein extent (Kappa =0.464).Conclusions The upregulation of 8-OHdG in the pterygium tissue indicates that oxidative damage of DNA plays a role in the development of pterygium.Oxidative damage of DNA caused by ultraviolet may be an upriver factor,which induces raising up of expression of bcl-2 and inhibits the apoptosis of normal cells and further proliferation of the conjunctiva tissue,resulting in the genesis and development of pterysium.

Imbalance of Oxidant/Antioxidant Status and Risk Factors for Saudi Type 2 Diabetic Patients with Retinopathy.

Aims: To estimate the oxidant/antioxidant status in type 2 diabetic patients with retinopathy; and to correlate a number of independent variables (age, gender, education, body mass index, duration of diabetes, glycosylated haemoglobin, hypertension) to development of retinopathy. Study design: Case-control study. Place and Duration of Study: Research laboratories, Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University from April 2010 to April 2011. Methodology: One-hundred diabetic patients with retinopathy recruited from King Fahad Specialist Hospital- Buraidah were included in the study. The control groups were: control group 1 consisted of sixty type 2 diabetic patients without retinopathy recruited from Diabetes and Endocrinology Center, KFSH, Buraidah, KSA; and control group 2 consisted of sixty healthy "non diabetic subjects" recruited from public places, i.e. Estarahes (party lounges). Plasma, serum, and erythrocyte lysate were prepared from blood of each subject. Human serum 8-OHdG, plasma MDA, and erythrocyte lysate Cu-Zn SOD were estimated by using commercial kits supplied by Northwest, U.S.A. Data was analyzed using SPSS software and Win Episcope software. P- values < 0.05 were considered significant. Results: Age, education, duration of diabetes, poor glycaemic control, and hypertension were consistently associated with development of retinopathy (OR 5.891, 4.44, 10.420, 1.699, 1.820 respectively). Moreover, increased plasma MDA, increased serum 8-OHdG levels, decreased Cu-Zn SOD activity were observed in diabetic patients with retinopathy compared to subjects in control groups. In addition, negative correlations were found between plasma MDA and Cu-Zn SOD activity, HbA1c & Cu-Zn SOD activity as well in all subjects. Conclusion: This report emphasizes the important role of oxidative stress in the development of retinopathy in type 2 diabetes suggesting that blocking of oxidative stress is a crucial step for delayed progression of diabetic retinopathy and hence the need for antioxidant supplements to postpone the severity of diabetic retinopathy.

Effects of hydrogen saturated saline on the lung after paraquat poisoning / 中华急诊医学杂志

Objective To investigate protective effects of the hydrogen saturated saline on acute lung injury and pulmonary fibrosis in rats with paraquat (PQ) poisoning. Method Forty-eight Sprague-Dawley rats were randomly divided into 3 groups, namely control group, PQ poisoning group and intervention group (n = 16 rats in each group) . Animals in PQ poisoning group and intervention group were fed with PQ in dosage of 50 mg / kg. Rats of control group were fed equivalent amount of distilled water instead. One hour after administration of PQ, rats of intervention group were treated with 5 ml / kg hydrogen saturated saline injected intra-peritoneally twice a day until the rats were sacrificed. The rats of poisoning group and control group were treated with intra-peritoneal injection of equivalent amount of normal saline. Arterial partial pressure of oxygen ( PaO2 ), 8-hydroxy-2' -desoxyguanosine (8-OHDG) and transforming growth factor β1 (TGF-β1) of lung tissue were measured on the 3rd and 21st day after PQ administration. Quantitative data was expressed as mean ±standard deviation (x-±s) . SPSS version 12. 0 package was applied for variance analysis and SNK-q test, and statistical differences were considered significant when P ＜ 0. 05. Results ① PaO2 decreased significantly in poisoning group (9. 34 ± 0. 47 kPa) and intervention group (10. 30±0.62 kPa) compared with control group (11.87 +/- 0.42 kPa) on the 3d (P ＜0.01), and as intervention group was compared with poisoning group, there was a significant difference ( P ＜ 0. 05 ) . On the 21st day, PaO2 was still lower in poisoning group (8. 36 ±0. 51 kPa) and intervention group ( 10. 14 ±0. 27 kPa) than that in control group ( 11.87 +0. 24 kPa) (P ＜0. 01 and P ＜0. 05, respectively), and as intervention group was compared with poisoning group, there was a significant difference ( P ＜ 0. 01 ) . ②The levels of 8-OHDG in lung tissue increased significantly in poisoning group (23.58±7. 18 ng/ml ) and intervention group (9. 49± 2. 45 ng/ml) on the 3rd day after PQ administration compared with control group (7.71 + 1.96 ng/ml) (P＜0. 01 and P＜0. 05, respectively), and as intervention group was compared with poisoning group there was a significant difference ( p ＜0. 01 ) . There were no significant differences in 8-OHDG level found among the groups on the 21st day after PQ administration (P ＞ 0. 05 ) . ③ The level of TGF-β1 (measured by mean optic density, MOD) in lung tissue of rats in poisoning group ( 10. 11±2.49 MOD) and intervention group (8. 14 + 1.58 MOD) exhibited in higher levels than control group (5.93 + 1. 98 MOD) on the 3rd and (5.97 + 2. 35 MOD) on the 21st day after PQ administration (P ＜0. 01 and P ＜0. 05, respectively), and however, a lower level of TGF-β1 was observed in intervention group on 3d and 21d compared with poisoning group (P ＜0. 05 and P ＜0. 01, respectively) . Conclusions Hydrogen saturated saline can alleviate oxidative stress, mitigate oxidative damage and inhibit pulmonary fibrosis of lung induced by PQ intoxication.