8-OHdG Expression Research Articles

Maternal Tn Immunization Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats Through Suppression of Oxidative Stress and Inflammation.

Hyperoxia therapy is often required to treat newborns with respiratory disorders. Prolonged hyperoxia exposure increases oxidative stress and arrests alveolar development in newborn rats. Tn antigen is N-acetylgalactosamine residue that is one of the most remarkable tumor-associated carbohydrate antigens. Tn immunization increases the serum anti-Tn antibody titers and attenuates hyperoxia-induced lung injury in adult mice. We hypothesized that maternal Tn immunizations would attenuate hyperoxia-induced lung injury through the suppression of oxidative stress in neonatal rats. Female Sprague–Dawley rats (6 weeks old) were intraperitoneally immunized five times with Tn (50 μg/dose) or carrier protein at biweekly intervals on 8, 6, 4, 2, and 0 weeks before the day of delivery. The pups were reared in room air (RA) or 2 weeks of 85% O2, creating the four study groups: carrier protein + RA, Tn vaccine + RA, carrier protein + O2, and Tn vaccine + O2. The lungs were excised for oxidative stress, cytokine, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression, and histological analysis on postnatal day 14. Blood was withdrawn from dams and rat pups to check anti-Tn antibody using western blot. We observed that neonatal hyperoxia exposure reduced the body weight, increased 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and lung cytokine (interleukin-4), increased mean linear intercept (MLI) values, and decreased vascular density and VEGF and PDGF-B expressions. By contrast, Tn immunization increased maternal and neonatal serum anti-Tn antibody titers on postnatal day 14, reduced MLI, and increased vascular density and VEGF and PDGF-B expressions to normoxic levels. Furthermore, the alleviation of lung injury was accompanied by a reduction in lung cytokine and 8-OHdG expression. Therefore, we propose that maternal Tn immunization attenuates hyperoxia-induced lung injury in neonatal rats through the suppression of oxidative stress and inflammation.

Suppression of Light-Induced Retinal Degeneration by Quercetin via the AP-1 Pathway in Rats.

We examined the cytoprotective effect of quercetin via activator protein (AP-1) and the heat shock protein 70 (Hsp70) pathway against light-induced retinal degeneration in rats. Quercetin was administered intraperitoneally to Sprague-Dawley rats for seven days before light exposure to intense white fluorescent light (3000 lux) for 24 h. Light-induced retinal damage was determined by the number of rows of photoreceptor cell nuclei, the microstructures of the rod outer segments and retinal pigment epithelium, and terminal deoxynucleotidyl transferase (TdT)-mediated 2′-Deoxyuridine-5′-triphosphate (dUTP) nick end labeling. To elucidate the cytoprotective mechanism of quercetin, expression levels were measured in the rat retinas of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative stress; Hsp70; and transcription factor AP-1 transcription activity. Pretreatment with quercetin inhibited light-induced photoreceptor cellular apoptosis and subsequent retinal degeneration in rats. 8-OHdG and Hsp70 protein expressions were up-regulated markedly by light exposure and suppressed by quercetin pretreatment. The results of an electrophoretic mobility shift assay showed that AP-1-binding activity was activated by light exposure, and binding of c-Fos and c-Jun, but not JunB, mediated the binding activity. Intraperitoneal administration of quercetin decreases photooxidative damage in the retina and mediates cytoprotection against light-induced photoreceptor cell degeneration in rats. Suppression of the heterodimeric combination of c-Jun and c-Fos proteins at the AP-1 binding site is highly involved in quercetin-mediated cytoprotection.

Standarized Tribulus terrestris extract protects against rotenone-induced oxidative damage and nigral dopamine neuronal loss in mice.

Strong evidence proposes that brain oxidative DNA damage and microglia activation contribute to Parkinson's disease (PD) pathogenesis. Traditional therapeutic regimens for PD can only relieve the symptoms. Tribulus terrestris (T. terrestris), a flowering plant from family Zygophyllaceae, is used in traditional medicine for treating different disorders and exerts neuroprotective and antioxidant effects in experimental models. The current study attempted to test whether treatment with T. terrestris standardized extract (TTE) can improve motor dysfunction and alleviate rotenone induced oxidative DNA damage and neurotoxicity in mice. Six groups of male Swiss albino mice were utilized. Group (1) was the vehicle (oil) group, group 2 was the rotenone control group (1 mg/kg/48 hours, subcutaneously) for 9 times, groups 3 and 4 were injected with rotenone and treated with TTE (5 or 10 mg per kg, by oral gavage) for 17 days, groups 5 and 6 served as TTE (5 or 10 mg per kg) per se groups. Motor function was measured by the pole and the open-field tests. Then, mouse brains were dissected, one hemisphere was employed for biochemical assays and the other one was used in histopathological studies. Results demonstrated that TTE ameliorated the motor dysfunctions induced by rotenone as well as markers of inflammation and DNA damage (8-OHdG and MTH1 expression). Indicators of oxidative stress and upregulation of the microglia marker (CD11b) were suppressed by the higher dose of TTE (10 mg per kg). Finally, the higher dose of TTE improved the Cresyl violet staining and tyrosine hydroxylase immunostaining in the substantia nigra. In summary, TTE ameliorated the locomotor dysfunction and dampened the DNA damage and oxidoinflammatory stress in rotenone-parkinsonian mice. These results suggest TTE as a potential candidate for neurodegenerative diseases.

Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats.

Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2′-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS expression was enhanced. The number of NT-positive cells was increased in MDMA-exposed animals, whereas no differences were detected in 8OHdG expression among experimental groups. MDMA and NT markers colocalized with DT1 positive cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no colocalization was observed with microglia and astrocytes. Moreover, MDMA immunostaining was not found in NOX2-positive cells. Our results suggest that iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of different enzymatic systems in the development of neuropathological alterations induced by the abuse of this psychoactive compound.

Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer.

BackgroundExposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC).MethodsWe investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking.ResultsThe expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05).ConclusionsThe expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.

Role of Histamine H₃ Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma.

Intraocular pressure (IOP) has a tendency to fluctuate throughout the day, reaching its peak in the early morning in healthy subjects or glaucoma patients. Likewise, histamine tone also fluctuates over time, being lower at nighttime. Numerous studies have demonstrated a correlation between short-term IOP fluctuation and glaucoma progression; however, it has not yet been determined whether histamine plays a role in IOP fluctuations. The aim of this research was to establish the distribution of the histamine receptor proteins and respective mRNAs in the eye by western blot, immunohistochemistry and RT-PCR in New Zealand rabbits. Furthermore, we used a transient ocular hypertension (OHT) model induced by injection of 50 µL of 5% hypertonic saline into the vitreous and a stable OHT model (100 µL 0.1% carbomer in the anterior chamber) to address the potential IOP-lowering ability of H3 receptor (H3R) antagonists (ciproxifan, DL76 and GSK189254). IOPs were performed with a Tono-Pen at baseline and 60, 120 and 240 min post treatment after transient OHT induction and, every day for 12 days in the stable OHT model. All histamine receptor subtypes were localized in the rabbit retina and ciliary body/trabecular meshwork. All the treatments lowered IOP in a dose-dependent fashion between 0.3% and 1%. More specifically, the effects were maximal with ciproxifan at 60 min post-dose (IOP60 change = −18.84 ± 4.85 mmHg, at 1%), remained stable until 120 min (IOP120 change = −16.38 ± 3.8 mmHg, at 1%) and decayed thereafter to reach baseline values at 240 min. These effects were highly specific and dependent on histamine release as pre-treatment with imetit (H3R agonist, 1%) or pyrilamine (H1R antagonist, 1%) largely blocked ciproxifan-mediated effects. Color Doppler ultrasound examination was performed to evaluate changes in ophtalmic artery resistivity index (RI) before and after repeated dosing with DL 76, GSK189254, ciproxifan and timolol. Chronic treatments with H3R antagonists and timolol improved the vascular performance of ophthalmic arteries and reduced retinal ganglion cell death. Oxidative stress was also reduced and measured 8-Hydroxy-2′-deoxyguanosine (8OHdG) expression, and by dihidroethydium (DHE) staining. These results demonstrated that the histamine system participates in IOP regulation and that H3R antagonists could represent a future promising therapy for glaucoma. Further studies should be focused on the long-term IOP circadian fluctuations.

Oxidative stress and LINE-1 reactivation in bladder cancer are epigenetically linked through active chromatin formation

Oxidative stress and reactivation of long interspersed element-1 (LINE-1) are coincidently observed in bladder cancer (BlCa), but the mechanistic connection between these two oncogenic phenomena is unknown. Previously, we reported increases in oxidative stress and LINE-1 protein (ORF1p) expression in human BlCa tissues. In this study, we measured 5-methylcytosine (5mC), 8-hydroxydeoxyguanosine (8-OHdG), 8-oxoguanosine DNA glycosylase-1 (OGG1), H3K9me3 and HP1α in bladder tissues obtained from BlCa patients. Reactivation of LINE-1 by reactive oxygen species (ROS) through chromatin remodeling was investigated in seven BlCa cell lines. We found that 5mC was decreased, but 8-OHdG, H3K9me3 and HP1α levels were increased in BlCa tissues relative to the adjacent non-cancerous tissues. OGG1, H3K9me3 and HP1α expression in BlCa tissues were positively correlated with 8-OHdG levels. Following H2O2 treatment, LINE-1 transcript expression was increased in VM-CUB-1 and TCCSUP, whereas AluYa5 and AluYb8 transcripts were increased in BFTC905 cells. Basal expression of LINE-1 ORF1p varied among BlCa cell lines from none to very high. H2O2 treatment clearly increased expression of ORF1p in VM-CUB-1, TCCSUP and BFTC905. Chromatin immunoprecipitation experiments revealed that 5′-LINE-1 promoters became further enriched in H3K4me3 and H3K18ac in VM-CUB-1 and BFTC905 cells treated with H2O2. In contrast, 5′-LINE-1 promoters became more enriched in H3K9me3 and H3K27me3 in UM-UC-3 treated with H2O2. In summary, decreased 5mC, but increased 8-OHdG, H3K9me3 and HP1α expression were demonstrated in human BlCa tissues, indicating global DNA hypomethylation, increased oxidative stress and altered histone methylation in BlCa. Chromatin structures were profoundly changed in BlCa cells exposed to ROS, but expression of LINE-1 transcript and protein were at most modestly increased. ROS enhanced expression of full-length LINE-1 elements only in cell lines with pre-existing activation, which was paralleled by increased formation of active chromatin at LINE-1 promoter loci.

Up-Regulation of Trem2 Inhibits Hippocampal Neuronal Apoptosis and Alleviates Oxidative Stress in Epilepsy via the PI3K/Akt Pathway in Mice.

Epilepsy is a chronic and severe neurological disorder that has negative effects on the autonomous activities of patients. Functionally, Trem2 (triggering receptor expressed on myeloid cells-2) is an immunoglobulin receptor that affects neurological and psychiatric genetic diseases. Based on this rationale, we aimed to assess the potential role of Trem2 integration with the PI3K/Akt pathway in epilepsy. We used microarray-based gene expression profiling to identify epilepsy-related differentially-expressed genes. In a mouse hippocampal neuron model of epilepsy, neurons were treated with low-Mg2+ extracellular fluid, and the protein and mRNA expression of Trem2 were determined. Using a gain-of-function approach with Trem2, neuronal apoptosis and its related factors were assessed by flow cytometry, RT-qPCR, and Western blot analysis. In a pilocarpine-induced epileptic mouse model, the malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) content and superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px) activity in the hippocampus were determined, and the protein expression of Trem2 was measured. In addition, the regulatory effect of Trem2 on the PI3K/Akt pathway was analyzed by inhibiting this pathway in both the cell and mouse models of epilepsy. Trem2 was found to occupy a core position and was correlated with epilepsy. Trem2 was decreased in the hippocampus of epileptic mice and epileptic hippocampal neurons. Of crucial importance, overexpression of Trem2 activated the PI3K/Akt pathway to inhibit neuronal apoptosis. Moreover, activation of the PI3K/Akt pathway through over-expression of Trem2 alleviated oxidative stress, as shown by the increased expression of SOD and GSH-Px and the decreased expression of MDA and 8-OHdG. The current study defines the potential role of Trem2 in inhibiting the development of epilepsy, indicating that Trem2 up-regulation alleviates hippocampal neuronal injury and oxidative stress, and inhibits neuronal apoptosis in epilepsy by activating the PI3K/Akt pathway.

The protective effects of astaxanthin against cisplatin-induced retinal toxicity

Purpose This study investigated the toxic effects of an antineoplastic agent, cisplatin (CIS), on retinal cells and the potential capacity of astaxanthin (ASTA) to elicit a future therapeutic protocol in CIS-induced retinal toxicity. Materials and methods Six groups were formed for the assessment; control (healthy; Group 1), olive oil (olive oil only; Group 2), ASTA control group (ASTA only, Group 3), the single intraperitoneal (IP) dose of 16 mg/kg CIS (CIS only group; Group 4), 16 mg/kg CIS +25 mg/kg (IP) ASTA (Group 5), and 16 mg/kg CIS +75 mg/kg (IP) ASTA (Group 6). On the third day after CIS administration, rats in all groups were sacrificed under anesthesia and the analysis of the biochemical parameters and histopathological levels were performed. Results A significant decrease in GSH levels and increases in MDA, eNOS, and 8-OHdG expressions were recorded. Additionally, CIS treatment had caused acidophilic staining in retinal histological appearance. ASTA treatment reduced the increases in MDA, eNOS, and 8-OHdG levels following CIS administration and increased the levels of GSH expressions, as well. Conclusions These results may suggest that the ASTA molecule as a promising option to prevent retinal toxicity in patients receiving CIS treatment for malignant tumors.

NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats

Presbycusis has become a common sensory deficit in humans. Oxidative damage to mitochondrial DNA and mitochondrial dysfunction is strongly associated with the aging of the auditory system. A previous study established a mimetic rat model of aging using D-galactose (D-gal) and first reported that NADPH oxidase-dependent mitochondrial oxidative damage and apoptosis in the ventral cochlear nucleus (VCN) might contribute to D-gal-induced central presbycusis. In this study, we investigated the effects of apocynin, an NADPH oxidase inhibitor, on mitochondrial dysfunction and mitochondria-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Our data showed that apocynin decreased NADPH oxidase activity, H2O2 levels, mitochondrial DNA common deletion, and 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity in the VCN of D-gal-induced aging model in rats. Moreover, apocynin also decreased the protein levels of phospho-p47phox (p-p47phox), tumor necrosis factor alpha (TNFα), and uncoupling protein 2 (UCP2) in the VCN of D-gal-induced aging model in rats. Meanwhile, apocynin alleviated mitochondrial ultrastructure damage and enhanced ATP production and mitochondrial membrane potential (MMP) levels in the VCN of D-gal-induced aging model in rats. Furthermore, apocynin inhibited cytochrome c (Cyt c) translocation from mitochondria to the cytoplasm and suppressed caspase 3-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Consequently, our findings suggest that neuronal survival promoted by an NADPH oxidase inhibitor is a potentially effective method to enhance the resistance of neurons to central presbycusis.

The effects of casticin and myricetin on liver damage induced by methotrexate in rats.

Objective(s): In this study, we evaluated the therapeutic effects of casticin and myricetin on liver damage induced by methotrexate in rats.Materials and Methods: Thirty-six male rats were used for the study and divided into 6 groups: control, methotrexate, casticin, myricetin, casticin+methotrexate, and myricetin+methotrexate. It was performed by methotrexate (20 mg/kg single dose, IP) in methotrexate, casticin+methotrexate and myricetin+methotrexate groups. Casticin 200 mg/kg dose was given to casticin and casticin+methotrexate groups. Myricetin 50 mg/kg dose was given to myricetin and myriceytin+methotrexate groups. At the end of the experiment, liver tissues were removed for the purpose of histopathological, biochemical and immunohistochemical assessments. Results:In our study, we have detected that MDA levels increased and activities of antioxidant enzymes SOD, CAT, and GPX decreased in the methotrexate group compared to the other groups, but the level of MDA decreased and activities of these enzymes increased in casticin+methotrexate and myricetin+methotrexate groups compared to the methotrexate group. In immunohistochemical examinations of control, casticin and myricetin groups in liver tissues no caspase-3 and 8-OHdG expressions were observed. In the MTX group, caspase-3 and 8-OHdG expressions were seen at the severe levels. Caspase-3 and 8-OHdG expressions were mild in hepatocytes in the casticin+methotrexate and myricetin+methotrexate groups. When the liver tissues of the rats in the methotrexate group were examined, severe pathological damage was detected both in the parietal region and in the portal region.Conclusion:By looking at these results, we can say that casticin and myricetin are effective against liver damage induced by methotrexate.

Integration of Nanostring Profiling and Functional Characterization of Oxidative and Replicative Stress Biomarkers Identifies Poor Prognosis MYC/BCL-2 Positive Diffuse Large B-Cell Lymphoma Subsets, Providing Opportunities for Precision Therapies

Integration of Nanostring Profiling and Functional Characterization of Oxidative and Replicative Stress Biomarkers Identifies Poor Prognosis MYC/BCL-2 Positive Diffuse Large B-Cell Lymphoma Subsets, Providing Opportunities for Precision Therapies

Antioxidant properties of topical Caulerpa sp. extract on UVB-induced photoaging in mice.

Caulerpa sp., a genus of seaweed native to the Indo-Pacific region, has been known for its antioxidant properties and health benefits when consumed as food. Previous studies have reported Caulerpa sp.’s potential as a strong antioxidant, but its effects on the skin in a topical preparation, especially its role in ultraviolet (UV) protection, have not been studied extensively. Our study investigated the protective effects of 0.2% and 0.4% Caulerpa sp. extract gels on photoaging in the UVB-irradiated skin of Wistar mice. The subjects were divided into naive control, vehicle control, and 3 treatment groups (0.2% Caulerpa sp. extract gel, 0.4% Caulerpa sp. extract gel, and 0.02% astaxanthin gel as a standard antioxidant). The groups, except the naive control group, received a total of 840 mJ/cm2 of UVB irradiation in four weeks. Protective effects of the extract were measured through the evaluation of collagen expression, matrix metalloproteinase (MMP)-1 expression and levels, and 8-OhDG expression. Mice who received topical application of Caulerpa sp. extract gel had higher collagen expression, better-preserved collagen structure, lower levels of MMP-1, and less MMP-1 and 8-OHdG expressions compared to the vehicle control group. There was no difference between different concentrations of the extract. Our findings demonstrated that topical application of Caulerpa sp. extract gel significantly protected UVB-irradiated mice skin from photoaging.

Thioredoxin-interacting protein deficiency ameliorates kidney inflammation and fibrosis in mice with unilateral ureteral obstruction

Thioredoxin-interacting protein (TXNIP) is associated with inflammation, tubulointerstitial fibrosis, and oxidative stress in diabetic kidney disease, yet the potential role of TXNIP in nondiabetic renal injury is not well known. This study aimed to investigate the effect of TXNIP on renal injury by creating a unilateral ureteral obstruction (UUO) model in TXNIP knockout (TKO) mice. We performed sham or UUO surgery in 8-week-old TXNIP KO male mice and age and sex-matched wild-type (WT) mice. Animals were killed at 3, 5, 7, or 14 days after surgery, and renal tissues were obtained for RNA, protein, and other analysis. Our results show that the expression of TXNIP was increased in a time-dependent manner in the ligated kidneys. TXNIP deletion reduced renal fibrosis, apoptosis, α-SMA, TGF-β1 and CTGF expression, and activation of Smad3, p38 MAPK, and ERK1/2 in UUO kidneys. We also found UUO-induced renal F4/80+ macrophage infiltration, MCP-1 expression and activation of NF-κB and NLRP3 inflammasome were attenuated in TKO mice. Furthermore, our study revealed that TXNIP deficiency inhibited the expression of 8-OHdG, heme oxygenase-1 (HO-1) and NADPH oxidase 4 (Nox4) in UUO kidney. In summary, our study suggests that TXNIP plays a key role in the renal inflammation and fibrosis induced by UUO. Inhibition of TXNIP may be a strategy to slow the progression of chronic kidney diseases.This paper shows that thioredoxin-interacting protein (TXNIP) expression is significantly upregulated in kidneys after unilateral ureteral obstruction. TXNIP deficient mice showed significant protection from renal injury. The reduction in oxidative stress, interstitial inflammation, fibrosis, NLRP3 inflammasome activity and tubular cell apoptosis indicates that TXNIP may be a potential therapeutic target for renal fibrosis-associated kidney diseases.

Oxidative status of cardinal ligament in pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common and distressing health problem in adult women, but the pathophysiological mechanism is yet to be fully elucidated. Previous studies have indicated that oxidative stress may be associated with POP. Thus, the aim of the present study was to investigate the oxidative status of pelvic supportive tissue in POP and further demonstrate that oxidative stress is associated with the pathogenesis of POP. A total of 60 samples were collected from females undergoing hysterectomy for POP or cervical intraepithelial neoplasia (CIN). This included 16 females with POP II, 24 females with POP III–IV (according to the POP-Q system) and 20 females with CIN II–III as the control group. Immunohistochemistry was utilized to measure the expression of oxidative biomarkers, 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE). Major antioxidative enzymes, mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx1) were measured through reverse transcription-quantitative polymerase chain reaction, western blotting and enzyme activity assays. The results demonstrated that in the cardinal ligament, the expression of 8-OHdG and 4-HNE was higher in the POP III–IV group compared with the POP II group and control group. The MnSOD and GPx1 protein level and enzyme activity were lower in the POP III–IV group compared with the POP II or the control group, while the mRNA expression level of MnSOD and GPx1 was increased. In conclusion, oxidative damage is increased in the pelvic supportive ligament of female patients with POP and the antioxidative defense capacity is decreased. These results support previous findings that oxidative stress is involved in the pathogenesis of POP.

Detection of Se, Vit. E, Vit. A, MDA, 8-OHdG, and CoQ10 Levels and Histopathological Changes in Heart Tissue in Sheep with White Muscle Disease.

This study was carried out to determine vit. E, Se, vit. A, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and ubiquinone-10 (CoQ10) levels and histopathological changes in sheep with white muscle disease (WMD). A total of 30 sheep were used; 20 sheep with WMD were brought to our clinic for diagnosis and treatment at various times, and 10 healthy sheep were in the control group. The Se, vit. E, vit. A, MDA, 8-OHdG, and CoQ10 values of the healthy and WMD sheep were as follows: 0.917 ± 0.037, 0.790 ± 0.067; 1.190 ± 0.011, 1.090 ± 0.021; 5.400 ± 0.275, 5.200 ± 0.173; 1.602 ± 0.264, 2.636 ± 0.576; 0.656 ± 0.197, 1.485 ± 0.271; and 0.280 ± 0.044, 1.753 ± 0.551 respectively (p < 0.05). According to histopathological and immunohistochemical findings in the WMD group, hyaline degeneration, Zenker's necrosis, and dystrophic calcification were observed in the muscle fibers. Immunohistochemically, 8-OHdG staining of the heart tissue determined a severe 8-OHdG expression in the WMD group. The findings of this study suggest that MDA, 8-OHdG, and CoQ10 values could be used as diagnostic and prognostic biomarkers in sheep affected with WMD.

Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation.

Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. Novel and effective therapy is needed to prevent the secondary spread of damage beyond the initial injury. The aim of this study was to investigate whether berberine has a neuroprotective effect on secondary injury post-TBI, and to explore its potential mechanism in this protection. The mice were randomly divided into Sham-saline, TBI-saline and TBI-Berberine (50mg/kg). TBI was induced by Feeney's weight-drop technique. Saline or berberine was administered via oral gavage starting 1h post-TBI and continuously for 21 days. Motor coordination, spatial learning and memory were assessed using beam-walking test and Morris water maze test, respectively. Brain sections were processed for lesion volume assessment, and expression of neuronal nuclei (NeuN), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) were detected via immunohistochemistry and immunofluorescence. There were statistically significant improvement in motor coordination, spatial learning and memory in the TBI-Berberine group, compared to the TBI-saline group. Treatment with berberine significantly reduced cortical lesion volume, neuronal loss, COX-2, iNOS and 8-OHdG expression in both the cortical lesion border zone (LBZ) and ipsilateral hippocampal CA1 region (CA1), compared to TBI-saline. Berberine treatment also significantly decreased Iba1- and GFAP-positive cell number in both the cortical LBZ and ipsilateral CA1, relative to saline controls. These results indicated that berberine exerted neuroprotective effects on secondary injury in mice with TBI probably through anti-oxidative and anti-inflammatory properties.

Oxidative stress marker 8-hydroxyguanosine is more highly expressed in prostate cancer than in benign prostatic hyperplasia.

Oxidative stress is a primary cause of vascular endothelial damage. In the prostate, ischemia increases the levels of reactive oxygen species, growth factors and cytokines, and induces the development of angiogenesis, which results in cancer progression. The expression levels of an oxidative stress marker, 8-hydroxyguanosine (8-OHdG), were compared between prostate cancer and non-neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were significantly higher than those in benign prostatic hyperplasia (71.4% moderate and 28.6% strong; (p<0.01). Notably, 8-OHdG is expressed more highly in prostate cancer tissues in comparison to benign prostate tissues.

Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury

Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40years has yet been discovered. This study investigated the effects of cisplatin on the kidney, the damage mechanism involved, and the potential capacity of agents such as amifostine, curcumin, and melatonin to elicit a future therapeutic protocol in cisplatin-induced nephrotoxicity at the ultrastructural and molecular levels. Our study consisted of five groups: control (saline solution only; group 1), cisplatin (cisplatin only; group 2), cisplatin + amifostine (group 3), cisplatin + curcumin (group 4), and cisplatin + melatonin (group 5). Rats in all groups except the control group were administered a single intraperitoneal dose of 7.5mg/kg cisplatin. All animals were sacrificed under anesthesia on the sixth day after cisplatin administration. Cisplatin increased serum urea and serum creatinine levels and caused an increase in tubular necrosis scores (TNS), HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). Additionally, we observed basal membrane thickening in glomerules, intense electron deposition in the subendothelial region, and atypical folds in podocyte pedicels. Amifostine, curcumin, and melatonin reduced the increases in serum urea and serum creatinine levels following cisplatin administration and reduced the levels of TNS, HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). ROS-scavenging antioxidants may be a promising means of preventing acute kidney disease in patients using cisplatin in the treatment of malignant tumors.

Elevated levels of 8-OHdG and PARK7/DJ-1 in peri-implantitis mucosa.

Reactive oxygen species contribute to periodontal tissue homeostasis under control of anti-oxidative responses. Disruption in this balance induces severe inflammation and extended tissue degradation. Aim of this study was to identify the expression levels of nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2), Parkinsonism associated deglycase (PARK7/DJ-1), kelch-like ECH associated protein 1 (KEAP1), and 8-hydroxy-deoxyguanosine (8-OHdG) in peri-implant mucosal tissues affected by peri-implantitis, and to compare the levels to those of periodontally diseased and healthy tissue samples. Tissue biopsies were collected from systemically healthy, non-smoking 12 peri-implantitis patients, 13 periodontitis patients, and 13 periodontally healthy controls. Expression levels of NFE2L2/NRF2, PARK7/DJ-1, KEAP1, and 8-OHdG in tissue samples were analyzed immunohistochemically. Statistical analysis was performed by one-way ANOVA with Tukey's HSD test. Inflammatory cell infiltration in the connective tissue and loss of architecture in the spinous layer of the epithelium were prominent in peri-implantitis. Proportions of 8-OHdG and PARK7/DJ-1 expressing cells were elevated in both peri-implantitis (P = .025 for 8-OHdG and P = .014 for PARK7/DJ-1) and periodontitis (P = .038 for 8-OHdG and P = .012 for PARK7/DJ-1) groups in comparison with controls. Staining intensities of 8-OHdG and PARK7/DJ-1 were higher in the periodontitis and peri-implantitis groups than in the control (P < .01) groups. There was no difference in the expression levels of NFE2L2/NRF2 between the groups. KEAP1 was not observed in any tissue sample. Peri-implantitis is characterized by severe inflammation and architectural changes in the epithelium and connective tissue. The expressions of 8-OHdG and PARK7/DJ-1 are elevated in both peri-implantitis and periodontitis.