dinoprost and 8-hydroxyguanosine

Colorectal cancer as well as colorectal surgery is associated with increased oxidative stress through different mechanisms. In this study the levels of different oxidative stress markers were comparatively assessed in patients who underwent laparoscopic or conventional resection for colorectal cancer.. Sixty patients with colorectal cancer were randomly assigned to undergo laparoscopic (LS) or open surgery (OS). Lipid, protein, RNA, and nitrogen damage was investigated by measuring serum 8-isoprostanes (8-epiPGF2α), protein carbonyls (PC), 8-hydroxyguanosine (8-OHG), and 3-nitrotyrosine (3-NT), respectively. The primary end point of the study was to analyze and compare serum levels of the oxidative stress markers between the groups.. Postoperative serum levels of 8-epiPGF2α, 3-NT, and 8-OHG were significantly lower in the LS group at 24 h after surgery (p < 0.05). At 6 h postoperatively, the levels of 8-epiPGF2α and 3-NT were significantly lower in the LS group (p < 0.05). No difference in the levels of PC was found between the two groups at any time point. In the OS group, postoperative levels of 8-epiPGF2α were significantly lower than the preoperative values (p < 0.01). In the LS group, the postoperative values of 8-epiPGF2α, 3-NT, and 8-OHG were significantly lower than the preoperative values (p < 0.05).. Laparoscopic surgery for colorectal cancer is associated with lower oxidative stress compared to open surgery. 8-epiPGF2α was the most suitable marker for readily defining the oxidative status in patients who underwent surgery for colorectal cancer.

Topics: Aged; Analysis of Variance; Biomarkers; Colectomy; Colorectal Neoplasms; Dinoprost; Double-Blind Method; Female; Guanosine; Humans; Laparoscopy; Male; Oxidative Stress; Postoperative Period; Protein Carbonylation; Tyrosine

3-hydroxy-3-methylglutaric aciduria (HMGA) is an inherited disorder of the leucine catabolic pathway in which occurs a deficiency of the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme. Therefore, the organic acids 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA), mainly, accumulate in tissues of affected patients. Lately, much attention has been focused on free radicals as mediators of tissue damage in human diseases, causing lipid peroxidation, protein oxidation and DNA damage. The treatment of this disease is based in a restricted protein ingest and supplementation with l-carnitine (LC), an antioxidant and detoxifying agent. In the present work, we investigated the in vitro oxidative damage to DNA induced by the accumulation of organic acids and oxidative stress parameters in vivo of patients with 3-HMG, as well as the effect of the recommended therapy. The in vitro DNA damage was analyzed by the alkaline comet assay in leukocytes incubated with HMG and MGA (1 mM, 2.5 mM and 5 mM) and co-incubated with LC (90 μM and 150 μM). The in vivo urinary 15-F2t-isoprostane levels and urinary oxidized guanine species were measured by ELISA kits in patient's urine before and after the treatment with LC. HMG and MGA induced a DNA damage index (DI) significantly higher than that of the control group. The DI was significantly reduced in the presence of LC. It was also verified a significant increase of oxidized guanine species and urinary isoprostane levels, biomarker of oxidative DNA damage and lipid peroxidation respectively, in patients before treatment. After the treatment and supplementation with LC, patients presented significantly lower levels of those biomarkers. Analyzing the data together, we can conclude that HMGA patients present oxidative lipid and DNA damage, which is induced by HMG and MGA, and the antioxidant therapy with LC can prevent that kind of injuries.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetyl-CoA C-Acetyltransferase; Adolescent; Amino Acid Metabolism, Inborn Errors; Carnitine; Child; Child, Preschool; Dinoprost; DNA Damage; Guanine; Guanosine; Humans; Infant; Lipid Peroxidation; Meglutol

Morbid obesity leads to progressive failure of many human organs and systems; however, the role of oxidative damage to salivary composition is still unknown in the obese patients. In this study, we assessed the effect of bariatric surgery on oxidative damage in nonstimulated (NS) and stimulated (S) whole saliva. The study included 47 subjects with morbid obesity as well as 47 age- and gender-matched healthy volunteers. Oxidative modifications to lipids (4-hydroxynonenal (4-HNE) and 8-isoprostanes (8-isoP)), proteins (advanced oxidation protein products (AOPP) and protein carbonyl groups (PC)), and DNA (8-hydroxy-D-guanosine (8-OHdG)) were analyzed in morbidly obese patients before and after bariatric surgery as well as in the healthy controls. The concentrations of 8-isoP, AOPP, PC, and 8-OHdG were significantly higher in both NS and S of patients with morbid obesity than in the control patients and compared to the results obtained 6 months after bariatric surgery. The levels of oxidative damage markers were also higher in S versus NS of morbidly obese patients. In summary, morbid obesity is associated with oxidative damage to salivary proteins, lipids, and DNA, while bariatric treatment generally lowers the levels of salivary oxidative damage.

Topics: Adult; Advanced Oxidation Protein Products; Bariatric Surgery; Dinoprost; Female; Guanosine; Humans; Male; Middle Aged; Obesity, Morbid; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Saliva; Salivary Proteins and Peptides

Markers of oxidative stress and inflammation were analysed in the exhaled breath condensate (EBC) and urine samples of 14 workers (mean age 43  ±  7 years) exposed to iron oxide aerosol for an average of 10  ±  4 years and 14 controls (mean age 39  ±  4 years) by liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) after solid-phase extraction. Aerosol exposure in the workplace was measured by particle size spectrometers, a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS), and by aerosol concentration monitors, P-TRAK and DustTRAK DRX. Total aerosol concentrations in workplace locations varied greatly in both time and space. The median mass concentration was 0.083 mg m(-3) (IQR 0.063-0.133 mg m(-3)) and the median particle concentration was 66 800 particles cm(-3) (IQR 16,900-86,900 particles cm(-3)). In addition, more than 80% of particles were smaller than 100 nm in diameter. Markers of oxidative stress, malondialdehyde (MDA), 4-hydroxy-trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2α (8-isoprostane) and aldehydes C6-C12, in addition to markers of nucleic acid oxidation, including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU), and of proteins, such as o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr) were analysed in EBC and urine by LC-ESI-MS/MS. Almost all markers of lipid, nucleic acid and protein oxidation were elevated in the EBC of workers comparing with control subjects. Elevated markers were MDA, HNE, HHE, C6-C10, 8-isoprostane, 8-OHdG, 8-OHG, 5-OHMeU, 3-ClTyr, 3-NOTyr, o-Tyr (all p  <  0.001), and C11 (p  <  0.05). Only aldehyde C12 and the pH of samples did not differ between groups. Markers in urine were not elevated. These findings suggest the adverse effects of nano iron oxide aerosol exposure and support the utility of oxidative stress biomarkers in EBC. The analysis of urine oxidative stress biomarkers does not support the presence of systemic oxidative stress in iron oxide pigment production workers.

Topics: Adult; Aldehydes; Biomarkers; Breath Tests; Dinoprost; Ferric Compounds; Guanosine; Humans; Male; Malondialdehyde; Middle Aged; Nanoparticles; Oxidative Stress; Tandem Mass Spectrometry; Tyrosine

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

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Affect; Aged; Anticipation, Psychological; Caregivers; Case-Control Studies; Chronic Disease; Deoxyguanosine; Dinoprost; DNA Damage; Female; Guanosine; Humans; Hydrocortisone; Middle Aged; Oxidative Stress; Resilience, Psychological; Saliva; Secretory Rate; Spouses; Stress, Psychological; Surveys and Questionnaires

To assess novel liquid chromatography/mass spectrometric methods for measuring oxidative damage to nucleic acids and lipids, we compared urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 5-hydroxymethyl-2'-deoxyuridine (5-OHmU), and 8-hydroxyguanosine (8-OxoG), and an isoprostane, 8-iso-prostaglandin F(2)alpha (IsopF(2)alpha) in 234 healthy men (n = 113) and women (n = 121), 80 current smokers, 96 never-smokers), and 58 ex-smokers (no tobacco use for 3 years). The 8-OHdG and 8-OxoG did not differ significantly by group; 5-OHmU was higher in smokers, compared with ex- (p <.003) and never- (p <.0001) smokers and in ex- vs. never-smokers (p =.014) at, respectively, 13.5 +/- 0.7, 11.3 +/- 1.0, and 8.7 +/- 0.3 microg/g creatinine. IsopF(2)alpha was higher in smokers, compared with ex- (p =.007) and never-smokers (p <.0001) and in ex- vs. never- smokers (p =.002) at, respectively, 1.1 +/- 0.10; 0.74 +/- 0.07, and 0.51 +/- 0.04 microg/g creatinine. There were significant correlations among all three nucleic acid adducts and between IsopF(2)alpha and both 5-OHmU and 8-OHdG. Many smokers and ex-smokers had high levels of either 5-OHmU excretion or IsopF(2)alpha excretion, but not both. We conclude that 5-OHmU and IsopF(2)alpha are more discriminating of oxidative stress from tobacco smoke than the other two compounds measured. Whether characteristic patterns of excretion of these indicators forecast differential disease risk should be explored in future research.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Age Distribution; Aged; Aged, 80 and over; Chromatography, Liquid; Deoxyguanosine; Dinoprost; DNA Adducts; Female; Guanosine; Humans; Male; Mass Spectrometry; Middle Aged; Oxidation-Reduction; Oxidative Stress; Sex Distribution; Smoking; Thymidine