8-hydroxy-2--deoxyguanosine and Cataract

Diabetic retinopathy (DRP) is the formation of edema and small vessels in the retina due to high blood glucose levels. Asprosin is a hormone that stimulates the release of glucose from the liver into the circulation. Considering the relationship between oxidative stress and DRP, our study aimed to determine the levels of the oxidative stress markers 4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as asprosin, in the blood and aqueous humor (Aq) of patients with and without DRP.. Thirty patients with single-eye DRP and cataract (DRP + C), 30 patients with diabetes mellitus and cataract without DRP (DM + C), and 30 healthy control (CON) participants were enrolled into this retrospective study. Except for healthy controls, Aq and blood samples were taken from these patients during their cataract operation. Asprosin, 4-HNE, and 8-OHdG concentrations were analyzed using enzyme-linked immunosorbent assays.. In patients with DRP, the levels of asprosin, 4-HNE, and 8-OHdG were significantly higher in both Aq and blood samples compared with the group of patients without DRP.. These findings suggest that the measurement of asprosin, 4-HNE, and 8-OHdG levels may support clinicians in determining the risk of DRP development.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aldehydes; Aqueous Humor; Biomarkers; Cataract; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Fibrillin-1; Humans; Male; Middle Aged; Oxidative Stress; Retrospective Studies

To investigate whether a single nucleotide polymorphism (SNP) rs1136410 in the poly (ADP-ribose) polymerase-1 (PARP-1) gene was associated with PARP activities, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, and the risk of age-related cataract (ARC) in a Chinese Han population.. In this two-stage case-control study with a total of 1010 ARC patients and 1045 controls, SNP rs1136410 was genotyped by high-resolution melting analyses (HRM). PARP activities and 8-OHdG levels in peripheral blood mononuclear cells (PBMCs) were determined by ELISA kits.. In discovery, replication, and their merged sets, the variant genotypes (AG+GG) of SNP rs1136410 were significantly associated with an increased risk of ARC under a dominant model (Adjusted odds ratio (OR)=1.42, P. This study suggests that SNP rs1136410 may confer susceptibility to ARC by affecting PARP activities and oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Asian People; Case-Control Studies; Cataract; China; Deoxyguanosine; DNA Damage; Female; Genetic Association Studies; Genotype; Humans; Male; Middle Aged; Poly (ADP-Ribose) Polymerase-1; Polymorphism, Single Nucleotide; Risk Factors

To evaluate the changes of oxidative DNA damage (in the form of 8-OHdG) and three key DNA base-excision repair (BER) proteins, human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1) and DNA polymerase β (Pol β), in lens epithelium cells (LECs), cortex and nucleus of lenses with age-related cataract (ARC) and age-matched controls.. A total of 90 patients with ARC and 21 control subjects were enrolled. The samples included the anterior lens capsules (mainly composed of LECs) and various portions of lens. An ELISA assay was used to assess the 8-OHdG levels of genomic DNA extracted. Immunofluorescence and Western blot were used to analyze the localization and quantification of three BER proteins, respectively.. The 8-OHdG levels in lenses with ARC were higher than those of controls, and were not different among ARC subtypes. The 8-OHdG levels were the highest in the nucleus, followed by the LECs and cortex. The repair proteins were predominantly detected in the cellular nuclei of the LECs and superficial cortical cells. In the LECs, the protein levels of the three BER enzymes were higher in ARC than in controls. In the cortex, a downward trend of the levels of three BER enzymes was found with the increasing opaque degrees. In the nucleus, no enzymes were detected.. Our findings indicate that the oxidative DNA damage increases in lenses with ARC, and the three BER enzymes compensatively increase in the LECs, while decreasing in the opaque cortex. The results suggest that the oxidative DNA damage may be related ARC and the alteration of DNA repair enzyme levels in ARC is associated with the location and opaque degrees of lens.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aging; Blotting, Western; Cataract; Deoxyguanosine; DNA Damage; DNA Glycosylases; DNA Polymerase beta; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation; Humans; Lens, Crystalline; Male; Oxidative Stress

To evaluate DNA damage markers and the antioxidant status of serum and aqueous humor in glaucoma patients.. Aqueous humor and serum samples were obtained at the time of surgery from 28 patients with glaucoma and 27 patients with cataracts. Total antioxidant status (TAS) and 8-hydroxy-2´-deoxyguanosine (8-OHdG) levels of all samples were determined by spectrophotometric and enzyme-linked immunosorbent assay methods.. Aqueous levels of 8-OHdG were higher in glaucoma patients than in the cataract group (4.61±2.97 ng/ml versus 1.98±0.70 ng/ml, p=0.002). Serum levels of 8-OHdG were also higher in glaucoma patients than in the cataract group (17.80±8.06 ng/ml versus 13.63±3.54 ng/ml, p=0.046). The TAS levels of serum (0.55±0.13 mmol/lit versus 0.70±0.14, p=0.001), and aqueous humor (0.23±0.13 mmol/lit versus 0.34±0.15, p=0.001) in glaucoma patients were lower than in cataract patients.. Our findings provide evidence that oxidative DNA damage increases and TAS decreases in the serum and aqueous humor of glaucoma patients. These findings support the hypothesis that the formation of reactive oxygen species and/or a decrease in TAS may have an important role in the pathogenesis of glaucoma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Antioxidants; Cataract; Cross-Sectional Studies; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Glaucoma; Humans; Male; Middle Aged; Models, Statistical; Oxidative Stress; Spectrophotometry

This study examines the levels of oxidative damage in patients with cataract.. Blood samples were collected from 60 patients with cataract and 60 age- and gender-matched healthy individuals to measure 8-hydroxy 2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels.. A significant difference was observed in leukocyte 8-OHdG levels in patients with cataract in comparison with healthy persons (p < 0.001). Similarly, a significant difference was observed in plasma MDA levels in patients with cataract in comparison with healthy persons (p<0.001). In addition, a significant correlation was found between levels of 8-OHdG in leukocyte DNA and plasma MDA (r = 0.859, p < 0.001).. This study measured the oxidative DNA damage by measuring the 8-OHdG in the leukocyte DNA in patients with cataract. In addition, the level of MDA - a marker for lipid peroxidation - was measured to determine lipid peroxidation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aging; Cataract; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA Damage; Female; Humans; Leukocytes; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Reactive Oxygen Species

To compare age-related cataractous (ARC) changes in unirradiated mice lenses to those induced by head-only X-irradiation of 3 month-old mice.. lens epithelial cells (LECs) as well as partially degraded cortical DNA were visualized in fixed sections using 4',6-diamidino-2-phenylindole (DAPI) staining, and in fresh lenses using the vital stain Hoechst 33342. reactive oxygen species (ROS) activity was also visualized directly in fresh lenses using the vital dye Dihydrorhodamine (DHR). In fixed lenses an antibody specific for 8-OH Guanosine (8-OH-G) lesions was used to visualize DNA oxidative adducts from ROS damage. Alpha smooth muscle actin was visualized using specific antibodies to determine if myofibroblasts were present. Fluorescence was quantified using Laser Scanning Confocal Microscopy (LSCM). The degree of lens opacity and cataract formation was determined by slit lamp, or from digitalized images of light reflections taken with a low magnification light microscope.. Using DNA- and ROS-specific vital fluorescent dyes, and laser scanning confocal microscopy we have previously described 4 changes in the aging rodent lenses: 1) a significantly decreased density of surface LECs in lenses from old compared to younger mice and rats; 2) a very large increase in retained cortical nuclei and DNA fragments in the secondary lens fibers of old rodent lenses; 3) increased cortical ROS in old rodent lenses; 4) increased cataract concomitantly with the cortical DNA and ROS increases. In the current study we report that these same 4 changes also occur in an accelerated fashion in mice given head-only X-irradiation at 3 months of age. In addition to vital staining of fresh lenses, we also examined sections from fixed eyes stained with DAPI or hematoxylin and eosin (H&E) and found the same loss of surface LECs and accumulation of undigested nuclei and debris in secondary lens fibers occur with age or following X-irradiation. In addition sections from fixed-eyes were examined for ROS damage to DNA with antibodies specific for 8-OH-G lesions. The frequency of 8-OH-G lesions increased dramatically in lenses from old unirradiated mice over 24 months of age, and similarly in X-irradiated lenses by 9-11 months post irradiation. The accumulation of cortical nuclei was not the result of conversion or invasion by myofibroblasts as tested by antibodies to a marker for such cells, alpha smooth muscle actin.. X-irradiation damage induces a large decrease in surface LECs over a period of 3-11 months post X-irradiation of young mice. These changes are similar in extent to those seen in 24-29 months-old control mouse lenses with age-related cataracts. In 24+ month-old unirradiated mice the secondary lens fibers are not able to degrade nuclei or nuclear DNA efficiently and accumulate large numbers of cortical nuclei and nuclear fragments as well as ROS and 8-OHG lesions. X-irradiated lenses develop the same abnormalities in a more accelerated fashion. The extensive loss of LECS and accumulation of undegraded nuclei, ROS, and ROS damage may play a causal role in cataract generation in both unirradiated old mice and in previously irradiated young adult mice.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Cataract; Cell Count; Deoxyguanosine; DNA; Epithelial Cells; Female; Indoles; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Mice; Mice, Inbred C57BL; Reactive Oxygen Species; Staining and Labeling; Tissue Fixation; X-Rays

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aconitate Hydratase; Aging; Animals; Arteriosclerosis; Catalase; Cataract; Cell Nucleus; Deoxyguanosine; DNA; Female; Free Radicals; Heart Diseases; Humans; Hydrogen Peroxide; Longevity; Male; Mice; Mice, Transgenic; Mitochondria; Mitochondria, Heart; Muscle, Skeletal; Myocardium; Oxidation-Reduction; Oxidative Stress; Peroxisomes; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Superoxide Dismutase

We examined the ability of a pyridoxal-aminoguanidine adduct with both antiglycation and antioxidant activities in vitro to protect against neuropathy and cataract in streptozotocin-diabetic rats and compared the result with that of aminoguanidine. In vivo antiglycation and antioxidant activities were also compared between the adduct and aminoguanidine. Diabetic rats were given either of the compounds in their drinking water (9 mM) for 7 weeks. Neither compound affected body weight, blood glucose level or urine volume. The adduct, but not aminoguanidine, significantly improved motor nerve conduction velocity. The time to develop cataract was longer in adduct-treated rats than in untreated and aminoguanidine-treated rats. The increase in opacification of lenses in culture medium containing high glucose levels (55.5 mM) was more efficiently attenuated by the adduct than by aminoguanidine. Adduct and aminoguanidine similarly lowered glycated hemoglobin levels. The level of urinary 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, and the level of liver malondialdehyde plus 4-hydroxy-2-alkenals, a marker of tissue lipid peroxidation, both of which were elevated by diabetes, were significantly reduced by the adduct but not by aminoguanidine. These findings indicate that the pyridoxal-aminoguanidine adduct is superior to aminoguanidine in preventing diabetic neuropathy and cataracts, and we suggest that this may be at least partly due to the higher antioxidant activity of the former.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cataract; Deoxyguanosine; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dose-Response Relationship, Drug; Glucose; Glycated Hemoglobin; Guanidines; In Vitro Techniques; Lens, Crystalline; Lipid Peroxidation; Liver; Male; Motor Neurons; Neural Conduction; Pyridoxal; Rats; Rats, Wistar; Time Factors