Development of a colloidal gold based immunochromatographic strip for 8-OHdG detection / 生物工程学报

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive and stable biomarker for evaluating DNA oxidative damage. A rapid and sensitive colloidal gold immunochromatographic strip was developed for 8-OHdG detection by a competitive method. The sample pad (glass cellulose film), bonding pad (glass cellulose film), nitrocellulose film and absorbent pad were pasted on the polyvinyl chloride (PVC) base plate to construct the test strip. Colloidal gold (AuNPs) was prepared by the reduction of chloroauric acid with sodium citrate. 8-OHdG antibody (Ab) was coated on the outer layer of AuNPs to form Ab@AuNPs as a probe. Bovine serum albumin (BSA) and 8-OHdG were conjugated with carbodiimide hydrochloride to prepare an artificial antigen, which was used as the coating antigen of detection line. Goat anti mouse polyclonal antibody IgG was used as the coating antibody of control line. The experimental parameters were optimized including the type of nitrocellulose membrane, the formula of loading solution, and the spraying amount of gold labeled antibody. The results showed that the appropriate nitrocellulose membrane was CN 95. The optimal loading solution included BSA (1%), Tween-20 (3%), sucrose (3%) and NaCl (0.9%). The optimal spraying amount of gold labeled antibody was 4 μL. 8-OHdG can be detected by the strip under visible light, and the level of 8-OHdG in urine can be preliminarily determined by comparing the color intensity of T line and C line. The 8-OHdG concentration in urine was further calculated by the gray value of T line and the threshold of detection was 2.55 μg/L. This colloidal gold immunochromatographic strip is simple, rapid and specific for detecting 8-OHdG in human urine to preliminarily evaluate the human status.

Establishment and comparative analysis of three DNA damage models of GC-1 cells / 中国药理学通报

Aim To establish three kinds of DNA damage models of mouse testicular spermatogonia cell line GC-1 cells and analyze their similarities and differences. Methods GC-1 cells were treated with UVB irradiation, D-galactose(D-Gal) or bleomycin (BLM), respectively. Then the expression and localization of 'Y-H2AX were detected by Western blot and immunofluorescence, the expression and localization of 8-OHdG were measured by immunofluorescence, and the expression levels of p-p53 and p21 were measured by Western blot. Results The expression of -y-H2AX in GC-1 cell reached to the peak 4 h after UVB irradiation and 6 h after D-Gal stimulation, whereas -y-H2AX expression gradually increased after BLM stimulation, and the higher the concentration of BLM,the shorter the time to reach the peak. The results of immunofluorescence showed that 8-OHdG expression was observed in the nucleus and cytoplasm of GC-1 cells after UVB irradiation and BLM stimulation, and the longer the culture time, the more the expression in the nucleus. In contrast, the expression of 8-OHdG was observed in the cytoplasm and reached the peak at 6 h in the D-Gal stimulated GC-1 cells. After UVB irradiation, the protein expression levels of p-p53 gradually increased, while p21 protein expression appeared later than that of p-p53; in the D-Gal stimulated GC-1 cells, the protein expression levels of p-p53 reached the peak at 6 h, and p21 protein expression reached the peak at 12 h; after low concentration BLM stimulation, the protein expression levels of p-p53 and p21 continuously increased, and after high concentration BLM stimulation, the protein expression levels of p-p53 and p21 reached its peak at 2 h, then decreased at 4 h. Conclusions Three kinds of DNA damage models of GC-1 cells are successfully established, and the DNA damage in GC-1 cells treated with D-Gal is mild, while the DNA damage in GC-1 cells treated by UVB irradiation and BLM stimulation is more severe.

Relationship of brain-derived neurotrophic factor, malondialdehyde, and 8-Hydroxy 2-Deoxyguanosine with post-ischemic stroke depression / A relação do fator neurotrófico derivado do cérebro, malondialdeído e 8-hidroxi 2-desoxiganosina com a depressão pós-avc isquêmica

ABSTRACT A few studies have shown that serum brain-derived neurotrophic factor (BDNF) level in post-stroke depression is highly correlated with memory and neuropsychiatric disturbances. Objective: This study aimed to elucidate the relationship of serum BDNF, malondialdehyde (MDA), and 8-Hydroxy 2-Deoxyguanosine (8-OhdG) levels in acute stroke cases with one-month post-stroke depression. Methods: An observational study was conducted of 72 post-ischemic stroke patients in the Neurology ward of the Dr. M. Djamil Hospital, Padang, West Sumatra, Indonesia. Acute stroke (< 48 hours) serum BDNF, MDA, and 8-OhdG levels were measured using ELISA. Based on observations using the Hamilton Depression Rating Scale conducted one month after stroke, respondents were divided into two groups: with and without depression. The mean serum level was analyzed using the t-test and Mann-Whitney test, while differences in basic characteristics were analyzed using the Chi-square test. Multivariate analysis was conducted to determine the most significant factor associated with post-stroke depression. The error rate was set at 5%. Results: BDNF levels in acute stroke were significantly lower in the depression group than in the non-depression group (p < 0.05). MDA and 8-OhdG levels in acute stroke were higher in the depression group (p < 0.05). BDNF level during acute stroke was negatively correlated with post-stroke depression, while, conversely, acute stroke MDA and 8-OhdG levels were positively correlated with depression. Conclusion: BDNF had a negative correlation, while MDA and 8-OhdG had a positive correlation, with depression one-month post-stroke. 8-OhdG was the most influential factor in post-stroke depression.

RESUMO Alguns estudos mostraram que o nível sérico de fator neurotrófico derivado do cérebro (BDNF) na depressão pós-AVC está altamente correlacionado com a memória e com os distúrbios neuropsiquiátricos. Objetivo: Este estudo teve como objetivo elucidar a relação entre os níveis séricos de BDNF, malondialdeído (MDA) e 8-hidroxi 2-desoxiganosanos (8 OhdG) em casos de AVC agudo com depressão pós-AVC de um mês. Métodos: Um estudo observacional foi realizado em 72 pacientes com AVC pós-isquêmico na enfermaria de Neurologia do Hospital Dr. M. Djamil, Padang, Sumatra Ocidental, Indonésia. Os níveis séricos de BDNF, MDA e 8-OhdG no AVC agudo (< 48 horas) foram medidos usando ELISA. Com base nas observações da Hamilton Depression Rating Scale realizada um mês após o AVC, os entrevistados foram divididos em dois grupos: com e sem depressão. O nível sérico médio foi analisado pelo teste T e Mann-Whitney, enquanto as diferenças nas características básicas foram analisadas pelo teste do qui-quadrado. A análise multivariada foi realizada para determinar o fator mais significativo associado à depressão pós-AVC. A taxa de erro foi fixada em 5%. Resultados: O nível de BDNF no AVC agudo foi significativamente menor na depressão do que no grupo sem depressão (p < 0,05). Os níveis de MDA e 8-OhdG no AVC agudo foram maiores no grupo de depressão (p < 0,05). O nível de BDNF durante o AVC agudo foi negativamente correlacionado com os casos de depressão pós-AVC, enquanto, inversamente, os níveis de MDA e 8-OhdG do AVC agudo foram positivamente correlacionados com os casos de depressão. Conclusão: O BDNF tem uma correlação negativa, enquanto o MDA e o 8-OhdG tiveram uma correlação positiva com a depressão um mês após o AVC. 8-OhdG foi o fator mais influente na depressão pós-AVC.

Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice

ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor- at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-B (NF-B) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of -H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-B signaling pathway and inflammatory responses.

Effect of hOGG1 gene polymorphisms on urinary 8-OHdG level in occupational chromate exposed population / 中国职业医学

OBJECTIVE: To evaluate the genetic damage induced by occupational chromate exposure, and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1(hOGG1) polymorphisms and genetic damage in population with chromate exposure. METHODS: A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method, and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group. The whole blood chromium(WB-Cr) level was measured by inductively coupled plasma mass spectrometry. Urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization/time of flight mass spectrometry. RESULTS: The WB-Cr level was higher in the exposure group than that in the control group(meclian: 3.41 vs 0.90 μg/L, P<0.01). The urinary 8-OHdG level was higher in the exposure group compared with that in the control group(meclian: 6.02 vs 4.72 μg/g·creatinine, P<0.01). In study subjects(exposure group and control group), after adjusting the potential influencing factors such as age, body mass index(BMI), gender, smoking and drinking, chromate exposure might be a risk factor for increasing urinary 8-OHdG level(P<0.05), and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05). In chromate exposure group, the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05), while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level(P<0.05), after adjusting the potential influencing factors such as age, BMI, gender, smoking, drinking. However, after multiple Bonferroni correction tests, only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group(P<0.01). There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG(P<0.01). CONCLUSION: The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate. There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level.

Urine Malondialdehyde and 8-hydroxydeoxyguanosine Levels as Indices of Oxidative Damage in Patients with Atopic Dermatitis / 대한피부과학회지

BACKGROUND: The involvement of oxidative stress in the pathogenesis of various skin diseases has been suggested. OBJECTIVE: Urinary malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels served as indices of oxidative stress. We explored whether MDA and 8-OHdG levels were higher in patients with atopic dermatitis (AD) than in healthy controls. In addition, we evaluated the optimal cut-off values for 8-OHdG and MDA in the diagnosis of AD. We explored the associations between AD severity and the levels of serum IgE and oxidative products. METHODS: Urine samples were obtained from 52 AD patients and 27 healthy controls. We measured MDA levels (reflecting lipid oxidation) and 8-OHdG levels (reflecting DNA oxidation). Disease severity was assessed using the Scoring of Atopic Dermatitis (SCORAD) index. RESULTS: The urinary 8-OHdG level was 208.37±145.39 ng/mg Cr in AD patients and 115.65±63.95 ng/mg Cr in healthy controls. The urinary MDA level was 2.92±1.06 mmol/mg Cr in AD patients and 2.20±0.54 mmol/mg Cr in healthy controls. Both the urinary 8-OHdG and MDA levels were significantly higher in AD patients than in healthy controls (p=0.007, p=0.001, respectively). However, we found no correlation between disease severity or serum IgE and oxidative product levels. Levels of oxidative products did not differ significantly between children and adolescents and adults, males and females, or patients with intrinsic or extrinsic AD. CONCLUSION: MDA and 8-OHdG levels were higher in AD patients than in healthy controls. Oxidative stress may be involved in the pathophysiology of the disease.

Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients

Abstract Background: The major complications of “treated” Human Immunodeficiency Virus (HIV) infection are cardiovascular disease, malignancy, renal disease, liver disease, bone disease, and perhaps neurological complications, which are phenomena of the normal aging process occurring at an earlier age in the HIV-infected population. The present study is aimed to explore protein carbonyl content as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Objective: To investigate the potential of carbonyl content as a biomarker for detecting oxidative Deoxyribonucleic acid (DNA) damage induced Antiretroviral Theraphy (ART) toxicity and/or accelerated aging in HIV/AIDS patients. Methods: In this case–control study a total 600 subjects were included. All subjects were randomly selected and grouped as HIV-negative (control group) (n = 300), HIV-infected ART naive (n = 100), HIV-infected on first line ART (n = 100), and HIV-infected on second line ART (n = 100). Seronegative control subjects were age- and sex-matched with the ART naive patients and the two other groups. Carbonyl protein was determined by the method described in Levine et al. DNA damage marker 8-OH-dG was determined using 8-hydroxy-2-deoxy Guanosine StressXpress ELA Kit by StressMarq Biosciences. Results: Protein carbonyl content levels and oxidative DNA damage were significantly higher (p < 0.05) in HIV-infected patients on second line ART and HIV-infected patients on first line ART than ART naive patients and controls. In a linear regression analysis, increased protein carbonyl content was positively associated with increased DNA damage (OR: 0.356; 95% CI: 0.287–0.426) p < 0.05. Conclusions: Carbonyl content may has a role as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Larger studies are warranted to elucidate the role of carbonyl content as a biomarker for premature aging in HIV/AIDS patients.

Expression and significance of serum NSE, HCY and 8-in patients with acute cerebral infarction / 重庆医学

Objective To investigate the expression and significance of serum NSE,HCY and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the patients with acute cerebral infarction(ACI).Methods One hundred cases of ACI treated in the neurology department of this hospital from March 2013 to December 2015 were selected as the cerebral infarction group,and contemporaneous 100 persons undergoing healthy physical examination were selected as the control group.The cerebral infarction group were re-divided into three groups according to the infarction volume,the infarction area ＞ 10 cm3 as the large volume infarction group (L),5-10 cm3 as the middle volume infarction group (M) and ＜5 cm3 as the small volume infarction group (S).The levels of serum NSE,HCY and 8-OHdG were compared between the cerebral infarction group and the control group,and among the group L,M and S.The Pearson correlation test was adopted to conduct the correlation analysis between HCY,8-OHdG and NSE with the cerebral infarction volume,neural function deficit,and prognosis.Results The levels of Hcy,8-OHdG and NSE in the observation group were higher than those in the control group,the difference was statistically significant(P＜0.05);the levels of Hcy,8-OHdG and NSE in the group L were higher than those in the group M and S,the difference was statistically significant(P＜0.05);the Hcy,8-OHdG and NSE levels were positively correlated with the cerebral infarction volume and neurological deficit,and negatively correlated with the prognosis.Conclusion Serum NSE,HCY and 8-OH-dG levels are increased in the patients with ACI,moreover with the infarct volume increase,which are gradually elevated.Therefore serum NSE,HCY and 8-OHdG can be used to assess the severity and prognosis in ACI patients.

Effects of Wuzi Yanzong Prescription on cyclophosphamide-induced DNA damage of testis cells in mice / 中成药

AIM To investigate the effects of Wuzi Yanzong Prescription (Lycii Fructus,Cuscutae Semen,Rubi Fructus,Plantaginis Semen and Schisandrae chinensis Fructus) on DNA damage of testis cells in adult male mice induced by cyclophosphamide (CTX).METHODS Forty out of fifty adult male Balb/C mice were injected intraperitoneally with CTX and then were randomly and equally divided into model control group (normal saline),Wuzi Yanzong Prescription low-,medium-and high-dose groups (100,200 and 400 mg/kg),and the other ten mice served as normal control group (normal saline).All mice were anesthetized by inhalation of ether,and then were sacrificed by cervical dislocation.The sperm count,sperm motility and malformation rate of sperm were tested.The content of 8-hydroxy-deoxyguanosine (8-OHdG) in serum was measured using ELISA;the DNA damage degree of cells in testis was detected by single cell gel electrophoresis;the protein expressions of p-P53 and γ-H2AX in testis were examined by Western blot.RESULTS Compared with the model control group,Wuzi Yanzong Prescription groups showed significant increase in the sperm count,sperm motility and significantly decreased malformation rate of sperm,the level of 8-OHdG in serum,and the protein expressions of p-P53 and γ-H2AX in testis were also significantly decreased.CONCLUSION Wuzi Yanzong Prescription can significantly alleviate the DNA damage of testis cells in mice induced by CTX through down-regulating protein expressions of p-P53 and γ-H2AX.

Inhibitory effects of Huoxue Jiedu decoction on cellapoptosis via down-regulating 8-OhdG in obstructive nephropathy rats / 中国药理学通报

Aim To observe the effect of eplerenone(EPL) and Chinese decoction on cell apoptosis in obstructive nephropathy rats.Methods Sixty male Wistar rats were randomly divided into sham group, UUO group, EPL group and ZY group(n=15).Except sham group, the rats in the other groups were ligated with unilateral ureteral obstruction(UUO) for renal interstitial fibrosis model.The rats were treated with eplerenone at 100 mg·kg-1·d-1 added to diet in EPL group, and orally 13.7 g·kg-1·d-1 decoction of Chinese medicine in ZY group.The kidneys were harvested on 14th day, the number of renal cell apoptosis were detected by TUNEL, and serum aldosterone and 8-OhdG were detected with radioimmunoassay and ELISA.Caspase-12, caspase-9, Bax and Bcl-2 were examined by immunohistochemistry and Western blot.Results The levels of serum aldosterone, serum and urine 8-OhdG and the number of positive apoptotic cells increased significantly in UUO rats compared with Sham group.The overexpression of caspase-9, caspase-12 and Bax and down-regulated Bcl-2 were obvious in UUO group(P<0.01).The level of 8-OhdG, expression of caspase-9, caspase-12 and Bax were down-regulated, and Bcl-2 expression was up-regulated in eplerenone and Chinese decoction treated rats(P<0.01).Conclusion Eplerenone and Chinese decoction could inhibit cell apoptosis induced by oxidative damage after UUO via caspases and(or) Bax pathway.

Effects of Regular Treadmill Exercise on a DNA Oxidative-Damage Marker and Total Antioxidant Capacity in Rat Hippocampal Tissue

BACKGROUND AND PURPOSE: Regular exercise can result in changes in the levels of oxidative stress in the hippocampus; however, little attention has been paid to physical-activity-induced neuronal protection to exposure to lead compounds. This study investigated the effects of regular treadmill exercise on a DNA oxidative-damage marker [8-hydroxy-2'-deoxyguanosine (8-OHdG)] and the total antioxidant capacity (TAC) of hippocampal tissue in lead-acetate exposed rats. METHODS: This study investigated the effects of 8 weeks of regular treadmill exercise on 8-OHdG and the TAC of hippocampal tissue in lead-acetate-exposed rats. Wistar rats were randomly divided into four groups: baseline, sham (control), lead, and exercise+lead. The exercise program involved running on a treadmill with increasing intensity five times a week for 8 weeks. Animals in the lead and exercise+lead groups received lead acetate at 20 mg/kg body weight intraperitoneally three times weekly for 8 weeks. Animals in the sham group received solvent (ethyl oleate) at 30 mg/kg body weight three times weekly for 8 weeks. TAC and 8-OHdG were measured by spectrophotometric and ELISA techniques, respectively. Data were analyzed by ANOVA and Tukey's post-hoc test with a significance cutoff of p≤0.05. RESULTS: The level of 8-OHdG and the TAC were significantly higher and lower, respectively, in the lead group than in the baseline and sham groups (p<0.01). However, the 8-OHdG level and TAC value in hippocampal tissue were significantly decreased and increased, respectively, in the exercise+lead group relative to the lead group (p<0.05). CONCLUSIONS: The TAC of hippocampal tissue may be directly associated with neural protection mechanisms of exercise following lead acetate injection, and the beneficial effects of regular exercise in preventing hippocampal neuronal damage could be due to decreased hippocampal oxidative stress such as reflected by a lower 8-OHdG level and increased TAC.

8-Hydroxydeoxyguanosine (8-OHdG) levels in urinary samples of pesticide sprayers on exposure to organophosphorus pesticides.

Background: Free radicals and other reactive species are constantly generated in vivo and cause oxidative damage to biomolecules. DNA is probably the most biologically significant target of oxidative attack. Among numerous types of oxidative DNA damage the formation of 8-hydroxyguanosine (8-OHdG) is a sensitive biomarker of oxidative stress, an adduct formed as a result of biochemical reaction between ROS and DNA. Chronic exposure to Organophosphorus (OP) pesticides is implicated in many health conditions that result from the induction of oxidative stress, including cytogenetic damage. The main objective of the study was to evaluate the biochemical levels of 8-OHdG in spot urinary samples under the exposed OP pesticide sprayers and farm workers. Methods: In this study, 51 male pesticide sprayers and 39 farm workers in the age group of 18-47 years having exposure ranged from 3 to 15 years in duration were selected. The referents (n=31) were selected on the same criteria as well as they were never exposed to pesticides at any time. This study was conducted during the growing season (January, 2009 – September, 2010). The most commonly used OP pesticides like chlorpyriphos, Diazinon, Dimethioate, Monocrotofos etc., were used in this study. Urine samples from each participant were taken in sterile tubes and were stored at -200C till analysed. The concentration of 8-OHdG in samples were analyzed using ELISA. Results: The urinary levels of 8-OHdG were found to be significantly higher in the farm workers and pesticide sprayers in contrast to the level observed in the control group (p<0.05). When the data was analyzed in the exposed groups in relation to duration of exposure it was found that both the farm workers and sprayers who were exposed to OP pesticides for less than 5 years showed the maximum mean values of 8-OHdG in comparison to those exposed to for more than 10 years. Conclusions: In view of this regular bio monitoring studies in target human populations are imperative necessary due to frequent changes in pesticide formulations and introduction of newer pesticides. Despite that several life style factors may influence the urinary concentrations of 8-OHdG but still this non-invasive bio-marker 8-OHdG is preferred over other invasive techniques to evaluate the environmental and occupational exposure effect of OP pesticides on the genotoxicity of the exposed workers.

The influence of Fasudil on oxidative stress in patients with early-stage diabetic nephropathy / 实用医学杂志

Objective To investigate the influence of Fasudil on oxidative stress in patients with early-stage diabetic nephropathy. Methods 48 patients with earl-stage diabetic nephopathy were randomly divided into control group treated with Alpha-lipoic acid and treametn group with Fasudil. All patients were under strict control of blood glucose. Changes in the levels of serum cysc, urinal mALB and 8-OHdG were observed after two weeks treatment were compared between the two groups. Results Compared to pre-treatment, the content of serum cysc, urinal mALB and 8-OHdG were significantly decreased in both groups after treatment. There was no significant difference in the content of urine mAlb , CTGF and MCP-1 between the two groups before and after treatment (P > 0.05). Conclusion Fasudil may protect kidney through a mechanism by which the level of 8-OHdG in kidney is decreased and oxidative stress is alleviated.

Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.

Influence of tannic acid on contents of 8-OHdG and 3-NT in nephridial tissue of diabetic rats and supernatant of glomerular mesangial cells / 中国免疫学杂志

Objective:To observe the effect of tannic acid on renal morphology and function of diabetes mellitus model rats ,and to explore the mechanism of improving effect of tannic acid from oxidative stress , nitrosative stress angle.Methods: 8 rats were randomly selected from 68 6-week-old male Wistar rats as normal control group and the remaining 60 rats accepted high-sugar and high-fat diet for 4 weeks, then were injected streptozotocin ( STZ, 52 mg/kg ) intraperitoneally in order to manufacture a diabetic rat model.Further the diabetic rats were randomly divided into model group ,aminoguanidine group ,low-dose of tannic acid group and high dose of tannic acid group.The rats in aminoguanidine group were injected aminoguanidine [AG,40 mg/(kg· d)] intraperitoneally, those in low-dose of tannic acid group were injected tannic acid [TA,20 mg/(kg· d)] and those in high-dose of tannic acid group were injected tannic acid [TA,30 mg/(kg· d)].The rats in normal control group and model group were injected normal saline [NS, 30 mg/(kg· d)] and all rats were sacrificed and tissues were derived at the end of the week 10.Morphologic changes of kidney in diabetic rats were observed by HE staining and correlative biochemical indices of renal function were detected by biochemical analyzer.8-hydroxy deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT) content of renal tissue in rats in different groups were detected by ELISA method.Mesangial cells cultured in vitro were treated with high concentration of glucose (30 mmol/L) and AGEs (250 mg/L) and at the same time with different concentration of tannic acid (10,20,40 and 80μmol/L) on the basis of setting corre-sponding control group.The contents of 8-OHdG and 3-NT in the culture supernatant were measured by ELISA method after 48 hours.Results:Tannic acid can effectively improve the renal pathological changes and improve renal function of diabetic rats .The contents of 8-OHdG and 3-NT in kidney tissue homogenate of diabetic rats and in the supernatant of GMC cultured with high glucose or AGEs were all significantly increased and can be reduced by tannic acid.Conclusion:Tannic acid improving the structure and function damage of kidney in diabetic rats might be achieved by oxidative stress and nitrosative stress mechanism .

Association between dyslipidemia and 8-OHdG/Cr among a population exposed to chronic arsenic / 中华流行病学杂志

Objective To explore the association between dyslipidemia and the level of 8-OHdG/Cr in urine among a population exposed to chronic arsenic.Methods Four hundred and seven subjects were randomly selected in an arsenic-affected area in Inner Mongolia.After blood biochemical examination,all the subjects were divided into 4 groups based on the results of total cholesterol (TC),triglycerides (TG),high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C).The groups consisted of hypercholesterolemia,HDL-C ratio anomaly,combined hypercholesterolemia and HDL-C ratio anomaly,as well as a normal lipid group.Urine samples were collected and 8-OHdG/Cr was measured using the ELISA method.A generalized linear mixed model was used to analyze the association between dyslipidemia and 8-OHdG/Cr.Results The levels of 8-OHdG/Cr as 55.73 (39.90-79.94) ng/mg,58.08 (44.94-69.91) ng/mg,65.28 (49.29-92.95) ng/mg and 51.43 (36.86-68.57)ng/mgin the HDL-C ratio anomaly,hypercholesterolemia,combined hypercholesterolemia and HDL-C ratio anomaly groups and the control group,respectively,which showed significant differences on the levels of 8-OHdG/Cr in the four groups (P=0.006).From the linear regression analysis results showed that the 8-OHdG/Cr level incombined hypercholesterolemia and HDL-C ratio anomaly group was higher (4.25 ± 0.55 ng/mg) than in the control group (3.96 ± 0.55 ng/mg) (P=0.018).After adjusting for important covariates,there was a linear trend between the levels of 8-OHdG/Cr and dyslipidemia (P=0.016).Conclusion Data from our study showed a linear relation between hypercholesterolemia,HDL-C ratio anomaly and the 8-OHdG/Cr level,suggesting that dyslipidemia was associated with oxidative DNA damage among those arsenic-affected people.

Relationship between the functional single nucleotide polymorphism rs1052133 in the 8-oxoguanine DNA glycosylase 1 (OGG1) gene and vitiligo in a Chinese Han population / 中华皮肤科杂志

Objective To estimate the relationship of the functional single nucleotide polymorphism (SNP) rs1052133 in the 8-oxoguanine DNA glycosylase 1 (OGG1) gene with vitiligo in a Chinese Han population.Methods Blood samples were collected from 800 patients with vitiligo and 800 healthy human controls,and subjected to genomic DNA extraction.PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the genotype of the SNP rs1052133 in the OGG1 gene.The relationship between the SNP and the risk of vitiligo was evaluated by chi-square test and unconditional logistic regression analysis.Enzyme linked immunosorbent assay (ELISA) was carried out to assess the serum level of 8-hydroxydeoxyguanosine (8-OHdG) in 83 patients with vitiligo and 83 healthy human controls,then,t test was used to compare the serum 8-OHdG level between the patients and controls.Results The frequency of CC,CG and GG genotype of the SNP rs1052133 was 16.8％,54.0％ and 29.2％ respectively in the patients,21.4％,52.8％ and 25.8％respectively in the controls (x2 =6.26,P ＜ 0.05).Increased frequency of G allele of the SNP rs1052133 was observed in the patients with vitiligo compared with the controls (56.2％ vs.52.2％,x2 =5.16,P ＜ 0.05).A statistically increased risk of vitiligo was associated with the CG (x2 =3.98,P ＜ 0.05,adjusted odds ratio 1.31,95％ confidence interval:1.01-1.70) and GG (x2 =6.01,P ＜ 0.05,adjusted odds ratio 1.45,95％ confidence interval:1.08-1.94) genotype of SNP rs1052133 compared with the CC genotype,which was more evident among the patients with the following characteristics:female,nonsegmental vitiligo,active vitiligo,long clinical course (＞ 12 months),a family history of vitiligo,and no accompanied autoimmune diseases.In addition,the patients with the CG or GG genotype of SNP rs1052133 had a higher serum 8-OHdG level than those with the CC genotype ((838.23 ± 294.11) μg/L vs.(593.84 ± 190.14) μg/L,t =3.63,P ＜ 0.01).Conclusions The SNP rs1052133 in the OGG1 gene may be responsible for the development of vitiligo in Chinese Han populations,which is likely to be associated with defects in DNA repair.

Determinants of oxidative stress and DNA damage (8-OhdG) in squamous cell carcinoma of head and neck.

Background: Squamous cell carcinoma of head and neck (SCCHN) is a major concern of health risk in developing countries, such as India. Apart from genetic configuration, environmental and lifestyle factors, as well as poor oral hygiene, provide free radical-generating environment, which may contribute to the development of cancer through DNA damage. Materials and Methods: Here we ascertained the various oxidative stress determinants in diagnosed SCCHN patients with health risk addictions. This study further evaluated the incremental effects inflicted by these lifestyle factors on redox status. The study included 100 consenting SCCHN patients and 90 matched healthy controls. Salivary total antioxidant capacity (TAC), glutathione (GSH), free radicals: such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) along with oxidative DNA adduct (8-OHdG) were monitored. Results: Our findings indicated altered salivary oxidant-antioxidant status in SCCHN. A substantial rise in ROS (~2.0 folds) and RNS (~1.4 folds), together with significant lowering in TAC (~1.2 folds) and GSH (~1.7 folds) was observed. The 8-OHdG levels were also found to be considerably higher (P < 0.001) in salivary cell's DNA of these patients. Conclusions: Our results demonstrate significant redox imbalance in cancer patients suggesting their paramount importance in the development of SCCHN.

Effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer.

Surgical resection at any location in the body leads to stress response with cellular and subcellular change, leading to tissue damage. The intestine is extremely sensitive to surgical stress with consequent postoperative complications. It has been suggested that the increase of reactive oxygen species as subcellular changes plays an important role in this process. This article focuses on the effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer. Mitochondrial DNA copy number, mitochondrial common deletion and nuclear and mitochondrial 8-oxo-2′-deoxyguanosine content were measured. Both the colon and rectal tissue were significantly damaged either at the nuclear or mitochondrial level. In particular, mitochondrial DNA was more damaged in rectum than in colon. The present investigation found an association between surgical stress and nuclear and mitochondrial DNA damage, suggesting that surgery may generate an increase in free radicals, which trigger a cascade of molecular changes, including alterations in DNA.

Saturated hydrogen saline protects rats from acute lung injury induced by paraquat / 世界急诊医学杂志（英文）

@#BACKGROUND: Paraquat (PQ) intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury (ALI) caused by paraquat poisoning. METHODS: Thirty PQ poisoned rats were randomly divided into a PQ intoxication group (intoxication group), a saturated hydrogen saline intervention group (intervention group), and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OhdG). Histological changes of the lungs were also observed. RESULTS: Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage (P<0.01 or P<0.05). However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage (P<0.01 or P<0.05). CONCLUSIONS: Saturated hydrogen saline is effective in preventing acute lung injury caused by PQ. Possibly, it can neutralize toxic oxygen radicals selectively and alleviate the oxidative stress injury induced by PQ.