4-hydroxy-2-nonenal and 8-hydroxyguanosine

Fibrillogenesis is a major feature of Alzheimer's disease (AD) and other neurodegenerative diseases. Fibers are correlated with disease severity and they have been implicated as playing a direct role in disease pathophysiology. In studies of tau, instead of finding causality with tau fibrils, we found that tau is associated with reduction of oxidative stress. Biochemical findings show that tau oxidative modifications are regulated by phosphorylation and that tau found in neurofibrillary tangles is oxidatively modified, suggesting that tau is closely linked to the biology, not toxicity, of AD.

Topics: Aldehydes; Alzheimer Disease; Animals; Guanosine; Humans; Mice; Nerve Degeneration; Neurofibrillary Tangles; Oxidative Stress; Phosphorylation; tau Proteins

Stallion-to-stallion variability in the quality of cryopreserved ejaculates postthaw affects the commercial acceptability of frozen semen and thus is a major constraint for the equine industry. In recent years, the molecular mechanisms associated with sperm damage during cryopreservation have become better understood. Identification of the freezability of the ejaculates before the freezing process is initiated will have a major impact on the equine industry. We studied three markers of oxidative stress in sperm, including 8-iso-PGF2alpha, 8-OH guanosine, and 4-hydroxynonenal (4-HNE); the presence of active caspase 3; and their changes after sperm cryopreservation. Although 4-HNE levels increased after cryopreservation (from 7% to 33%, P < 0.001), 8OH-guanosine and 8-ISO-PGF2alpha levels decreased after cryopreservation (from 130 to 35 arbitrary fluorescence units, P < 0.01, and from 1280 to 1233, P < 0.01, respectively). Postthaw sperm quality was classified as poor, average, or good using the 25th and 75th percentiles of all assays of sperm quality studied (motility, velocity, membrane functionality, and thiol content) as thresholds. Using these values, a sperm postthaw quality index was proposed. Receiver operating characteristic curves and the Youden J statistic were used to investigate the value of the measured parameters in fresh sperm as predictors of potential freezability. Using these techniques, we identified markers of bad freezers (percentages of caspase 3-positive dead sperm [area under the curve (AUC) = 0.820, P < 0.05] and percentages of caspase 3- and 4-HNE-positive sperm [AUC = 0.872, P < 0.05]) and good freezers (percentages of caspase 3-negative live sperm [AUC = 0.815, P < 0.05], percentages of live sperm with high thiol content [AUC = 0.907, P < 0.01], and percentages of 8-ISO-PGF2alpha-positive sperm [AUC = 0.900, P < 0.01]. Moreover, we described for the first time the presence of 8-ISO-PGF2alpha in stallion spermatozoa and revealed the importance of considering different markers of oxidative stress.

Topics: Aldehydes; Animals; Caspase 3; Cryopreservation; Dinoprost; Guanosine; Horses; Male; Oxidative Stress; Semen; Semen Preservation; Sperm Motility; Spermatozoa

Consumption of a high-fructose diet (HFrD) can induce the development of a metabolic syndrome, manifesting as nonalcoholic steatohepatitis (NASH) and/or type 2 diabetes mellitus (T2DM), via a process in which oxidative stress plays a critical role. Peroxiredoxin 4 (PRDX4) is a unique and only known secretory member of the PRDX antioxidant family. However, its putative roles in the development of NASH and/or T2DM have not been investigated.. To elucidate the functions of PRDX4 in a metabolic syndrome, we established a nongenetic mouse model of T2DM by feeding mice a HFrD after injecting a relatively low dose of streptozotocin. Compared with wild-type (WT), human PRDX4 transgenic (Tg) mice exhibited significant improvements in insulin resistance, characterized by a lower glucose and insulin concentration and faster responses in glucose tolerance tests. The liver of Tg also showed less severe vesicular steatosis, inflammation, and fibrosis, along with lower lipid concentrations, lower levels of oxidative stress markers, more decreased expression of hepatic aminotransferase, and more reduced stellate cell activation than those in the WT liver, reminiscent of human early NASH. Hepatocyte apoptosis was also significantly repressed in Tg mice. By contrast, serum adiponectin levels and hepatic adiponectin receptor expression were significantly lower in WT mice, consistent with greater insulin resistance in the peripheral liver tissue compared with Tg mice.. Our data for the first time show that PRDX4 may protect against NASH, T2DM, and the metabolic syndrome by ameliorating oxidative stress-induced injury.

Topics: Adiponectin; Aldehydes; Animals; Apoptosis; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Fatty Liver; Guanosine; Hepatocytes; Humans; Inflammation Mediators; Liver; Male; Mice; Mice, Transgenic; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Peroxiredoxins; Receptors, Adiponectin; T-Lymphocytes; Thiobarbituric Acid Reactive Substances

Non-alcoholic fatty liver disease is a common condition that can progress to endstage liver disease. The steatotic liver seems to be particularly susceptible to oxidative stress damage. The aim of this study was to evaluate the redox state in patients with non-alcoholic steatohepatitis (NASH) and its correlation with dietary intake.. Plasma concentrations of 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHdG), reduced and oxidized glutathione (GSH and GSSG), vitamins A and E, total antioxidant status (TAS), glutathione peroxidase (GSH-Px) and reductase (GSH-Red) erythrocyte activities were compared between 43 NASH patients and 33 healthy controls. 4-HNE, GSH-Px, GSH-Red and TAS were evaluated by spectrophotometry, 8-OHdG by ELISA assay, GSH and GSSG by fluorimetric assay and vitamins A and E by high performance liquid chromatography. Dietary habits were also evaluated in these patients.. GSH levels (21.1 +/- 18.3 versus 33.1 +/- 22.2 microM, p = 0.01) and GSH/GSSG ratio (0.9 +/- 0.7 versus 1.5 +/- 0.8, p = 0.01) were lower and TAS (832 +/- 146 versus 630 +/-140 microM, p < 0.001) and vitamin E (47.1 +/- 14.9 versus 34.5 +/- 7.3 microM, p < 0.001) were higher in NASH patients, although there was no difference in GSH-Px and GSH-Red activities, 8-OHdG and 4-HNE levels between groups. After adjusting for total energy consumption, a negative correlation was found with total and saturated fat intake and GSH/GSSG ratio, and a positive correlation with carbohydrates, fiber, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), specifically N-3 PUFA, and vitamins E, C, selenium and folate.. Our data suggest an impaired glutathione metabolism towards an oxidant status in NASH patients, correlating with a higher intake of saturated fat and a lower intake of carbohydrates. Plasmatic concentrations of oxidative stress cellular markers did not translate to hepatic oxidative damage.

Topics: Adult; Aged; Aldehydes; Diet; Dietary Carbohydrates; Dietary Fats; Erythrocytes; Fatty Liver; Female; Glutathione Peroxidase; Glutathione Reductase; Guanosine; Humans; Male; Middle Aged; Oxidative Stress; Vitamin E

Dentatorubral-pallidoluysian atrophy (DRPLA) is one of the CAG-repeat diseases, and is classified into juvenile and early adult types showing progressive myoclonus epilepsy (PME) in addition to late adult type. We immunohistochemically examined accumulation of oxidative products and expression of superoxide dismutase (SOD) in autopsy cases of DRPLA. Oxidative products to nucleosides, 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine, were accumulated in the lenticulate nucleus predominantly in DRPLA cases having PME. Neuronal accumulation of 4-hydroxy nonenal, a reactive lipid aldehyde, was found in the hippocampus, globus pallidus and cerebellar dentate nucleus in adult DRPLA cases and controls. Cytoplasmic immunoreactivity for Cu/ZnSOD was reduced in the external segment of globus pallidus, dentate nucleus and cerebellar cortex in DRPLA cases. Mitochondrial immunoreactivity for MnSOD was reduced in the lenticulate nucleus and cerebellum in DRPLA cases having PME. Some DRPLA cases showed reduced immunoreactivity for MnSOD in the cerebral cortex. Coexistence of reduced SOD expression and polyglutamine was observed in a few cases. It has been discussed in Huntington's disease that expanded polyglutamine can lead to oxidative neurodegeneration. It is likely that oxidative stress can be involved in DRPLA, although relationship with expanded polyglutamine remains to be elusive.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aldehydes; Autopsy; Biomarkers; Brain; Cytoplasm; Deoxyguanosine; Female; Guanosine; Humans; Immunohistochemistry; Male; Middle Aged; Mitochondria; Myoclonic Epilepsies, Progressive; Nerve Degeneration; Neurons; Oxidative Stress; Peptides; Superoxide Dismutase

Ethanol exposure during pregnancy may result in fetal alcohol syndrome (FAS). The mechanism by which this occurs is unknown. Recent studies in several organ systems, including the placenta, suggest that oxidative stress is involved. In this study we investigated the presence and levels of three oxidative stress markers in placental villous tissue exposed to ethanol.. Villous tissues from normal placentas were perfused with Dulbeco's modified Eagle's medium (DMEM) with HEPES buffer, sodium bicarbonate, and glucose at pH 7.4. After stabilization, 100 mM ethanol was added to the perfusate. After 2 hours of perfusion, the tissue was removed, fixed and stained for nitrotyrosine, 4-hydroxy-2-nonenal (4HNE) and 8-hydroxyguanosine (8-OHDG). Staining within the trophoblasts was quantified with densitometry.. Nitrotyrosine and 4HNE immunostaining was seen in the trophoblasts. 4HNE was also seen in the stroma. In contrast, 8-OHDG was seen only in the stroma and endothelial cells in the fetal circulation. Ethanol exposure significantly increased nitrotyrosine levels in the trophoblasts beyond levels in the control tissue. Nitrotyrosine and 8-OHDG levels were also increased in stroma.. Within the placental villi, markers of oxidative stress are present in the trophoblasts and stroma after a short period of ethanol exposure. There is an increase in oxidative stress, primarily involving the nitric oxide pathway, in the trophoblasts as well as DNA damage in the stroma. Lipid peroxidation is not acutely changed in our 2-hour exposure window.

Topics: Aldehydes; Biomarkers; Ethanol; Female; Guanosine; Humans; Oxidative Stress; Placenta; Pregnancy; Trophoblasts; Tyrosine

Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated measles virus, showing inflammation, neuronal loss, and demyelination. We neuropathologically examined six autopsy cases of subacute sclerosing panencephalitis, using in situ nick end-labeling and immunohistochemistry. Both the neurons and glial cells in the cerebral cortex showed immunoreactive nuclei in the nick end-labeling in two cases with disease duration within 2 years, whereas they were confined to the glial cells in the demyelinated cerebral white matter in three cases with disease duration ranging from 2 to 10 years. The nuclei and cytoplasm were immunoreactive for 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine, markers of oxidative damage to DNA and ribonucleic acid, respectively, in the cerebral cortex in three cases with disease duration within 9 years. In contrast, 4-hydroxy-2-nonenal-modified proteins, products of lipid peroxidation, were deposited in the demyelinated white matters in four cases with disease duration longer than 9 years. In three cases with long survival, the expression of glial glutamate transporters was reduced in the cerebral cortex. It is speculated in subacute sclerosing panencephalitis that apoptosis and oxidative stress to DNA can contribute to the early neuronal damage, whereas lipid peroxidation and disturbed glutamate transport may be related to the subsequent neurodegeneration.

Topics: Adolescent; Adult; Aldehydes; Amino Acid Transport System X-AG; Autopsy; Cerebral Cortex; Child; Female; Guanosine; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Lipid Peroxidation; Male; Neuroglia; Neurons; Oxidative Stress; Subacute Sclerosing Panencephalitis; Time Factors

Recently we reported that the supplementation of vitamin B6 to low vitamin B6 diet caused suppression in colon tumorigenesis and cell proliferation of azoxymethane-treated mice in a dose-dependent manner among 1, 7, and 14 mg pyridoxine HCl/kg diet (J. Nutr. 131: 2204-2207, 2001). To examine the mechanism of the anticolon tumor effect of vitamin B6, male ICR mice were fed the diet containing 1, 7, 14, and 35 mg pyridoxine HCl/kg diet for 22 wk and simultaneously given a weekly injection of azoxymethane for an initial 10 wk. The supplementation of vitamin B6 to a low vitamin B6 diet (1 mg pyridoxine HCl/kg) suppressed the levels of colonic 8-hydroxyguanosine and 4-hydroxynonenal and inducible nitric oxide synthase protein. The results suggest that the preventive effect of vitamin B6 against colon tumorigenesis is at least in part mediated by reducing oxidative stress and nitric oxide production.

Topics: Adjuvants, Immunologic; Aldehydes; Analysis of Variance; Animals; Azoxymethane; Carcinogens; Colonic Neoplasms; Cross-Linking Reagents; Guanosine; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Vitamin B 6