Urinary Total Antioxidant Capacity Research Articles

Shedding light on the shadows: oxidative stress and its pivotal role in prostate cancer progression.

Data on oxidative protein damage, total antioxidant capacity (TAC) and lipid peroxidation in progression of prostate cancer remain elusive. So far, the influence of the presence of perineural invasion on the level of oxidative stress has not been described. Additionally, there is limited data on the level of oxidative stress in patients' urine. We compared the levels of oxidative stress markers in serum and urine in 50 patients with prostate cancer depending on the tumor stage and histological grade, the Gleason score, and the presence of perineural invasion. We found a significantly de-creased level of serum thiol groups and TAC in participants with prostate cancer. Similarly, serum Amadori products and malondialdehyde (MDA) were higher in patients than in healthy men. There was a significantly decrease in TAC and a significantly increased MDA in the urine of prostate cancer patients. As the stage of cancer increased, a decrease in the thiol group concentration and TAC as well as an increase in the concentration of lipid peroxidation products in the serum was observed. The serum level of advanced oxidation protein products (AOPP) increased in the group with Gleason scores greater than 7. Furthermore, serum thiol groups and TAC were reduced in the group with Gleason >7 as compared to Gleason <7. The presence of perineural invasion significantly reduced serum and urinary TAC and increased urinary AOPP concentration. These results indicate a significant role for oxidative damage in prostate carcinogenesis and its progression. Characterizing oxidative and nitrosative damage to proteins may be useful in designing targeted therapies for prostate cancer patients.

Discriminating Different Bladder and Bladder Outlet Dysfunctions by Urinary Biomarkers in Women with Frequency–Urgency Syndrome

To investigate the role of urinary biomarkers in discriminating different bladder and bladder outlet dysfunctions in women with frequency-urgency syndrome. Urine samples collected from 146 women with frequency-urgency syndrome and 34 controls were investigated. All patients were included in previous clinical trials of functional urology studies and underwent a videourodynamic study. Patients with frequency-urgency syndrome were subdivided into idiopathic detrusor overactivity (IDO), neurogenic detrusor overactivity (NDO), dysfunctional voiding (DV), and hypersensitive bladder (HSB) subgroups. Urine samples were collected before any treatment, and urinary inflammatory proteins (interleukin- (IL-) 1β, IL-2, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)), neurogenic proteins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin E2 (PGE2)), and oxidative stress biomarkers (8-isoprostane, total antioxidant capacity (TAC), and 8-hydroxydeoxyguanosine (8-OHdG)) were measured and compared between the different OAB subgroups and controls. Of the 146 patients, 31 had IDO, 41 had NDO, 45 had DV, and 29 had HSB. The control group included 34 women. The patients with HSB had lower urinary TAC and IL-2 levels than the controls. The patients with IDO, NDO, and DV had significantly higher urinary TNF-α levels than those with HSB. The patients with IDO and NDO showed an increase in the urinary 8-isoprostane levels, whereas the patients with IDO had higher urinary IL-2, NGF, and BDNF levels than those with NDO. The other urinary inflammatory biomarkers did not show enough significant differences to discriminate between the different bladder and bladder outlet dysfunctions. The urinary levels of inflammatory, neurogenic, and oxidative stress biomarkers varied widely among the patients with bladder and bladder outlet dysfunction. This study's results provide evidence that women with frequency-urgency syndrome and different urodynamic subtypes have varying bladder inflammation and oxidative stress conditions, which might have an impact on treatment outcomes.

Urinary and Plasma Antioxidants in Behavioral Symptoms of Individuals With Autism Spectrum Disorder

The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2′-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.

Decreased Antioxidant Capacity in Corn Farmers Occupationally Exposed to the Mixture of Herbicides

Background: The application of herbicides has been a common practice in worldwide agriculture, mainlywith the goal to increase efficacy of weed control. So, most farmers faced a greater risk of herbicideexposure to develop adverse health effects from oxidative stress-induced herbicides. The aim of this studyis to determine the urinary total antioxidant capacity (TAC) and 8-isoprostane levels in farmers using themixture of herbicides in Long District, Phrae Province, Thailand.Methods: Ninety-three participants were recruited. The spot urine samples (pre- and post-work) werecollected. The urinary TAC was determined using ABTS radical scavenging assay. The urinary 8-isoprostanelevel was investigated by commercial ELISA kit.Results: Most farmers worked on a farm during 1-5 h/day. Fifty-five percents of participants used themixture of herbicide while working between glyphosate and paraquat as well as glyphosate and 2,4-D. Theurinary TAC levels in pre-work urine sample of farmers applied combining herbicides were significantlyhigher than that level in their post-work urine sample. However, there was no significant difference betweenpre- and post-work urinary 8-isoprostane in farmers applied combining herbicides.Conclusion: The results suggest that occupational exposure to mixture of glyphosate herbicides plus paraquator 2,4-D could induce abnormal oxidative stress value especially antioxidant defense among agriculturalworkers.

Effect of Coenzyme Q10 Supplementation on Urinary and Salivary Oxidative Stress Biomarkers in Bipolar Patients During the Depressive Episode

Background: Although depression is the predominant phase in Bipolar Disorder (BPD) and causes the most psychosocial disability, optimal pharmacotherapy of bipolar depression is not known yet. Advances in research on BPD neurobiology have demonstrated that oxidative toxic stress (OTS) may be involved in the pathophysiology of BPD. Objective: The present study aimed to evaluate the effects of adjuvant CoQ10, supplement with potent antioxidant properties, on salivary and urinary OTS biomarkers in patients with BPD during the depressive episode. Material and Methods: 89 BPD patients with current depressive episode were allocated into either CoQ10 (200 mg/day) or placebo group by block randomization method. The salivary and urinary levels of OTS biomarkers including Total Antioxidant Capacity (TAC) and DNA damage were measured at baseline and 8 weeks after treatment. Results: At baseline, urinary and salivary levels of TAC and DNA damage were statistically comparable between the two groups. After 8 weeks treatment with CoQ10, patients showed significantly higher increment in urinary TAC level compared to placebo, while salivary level of TAC did not display significant differences between the two groups. Although changes in salivary and urinary DNA damage levels were greater in CoQ10 group, the changes reached significant level only in the urine sample. Conclusion: Our findings suggest that CoQ10 can improve OTS status in BPD patients during depressive episode. As activation of oxidative stress is one of the mechanisms responsible for BPD, it seems that CoQ10 due to its proven antioxidant properties, as add on therapy to standard treatment may be a promising agent in treating bipolar depression.

Markers of oxidative stress and antioxidant status in the plasma, urine and saliva of healthy mice.

Oxidative stress markers are usually measured in plasma, a stable environment for biomarkers. Blood collection is invasive, but the use of alternative biofluids is limited, due to high variability. In this study, we aimed to establish reference values for oxidative stress markers in plasma, urine and saliva of adult, healthy mice and to identify some sources of variability. Samples were obtained from 41 female and 37 male adult, healthy mice of the CD-1 strain, aged 95-480 days, weighing 21-55 grams. Reference ranges of TBARS (thiobarbituric acid reactive substances), AOPP (advanced oxidation protein products), fructosamine, GSH/GSSG (reduced and oxidized glutathione) ratio, TAC (total antioxidant capacity), and FRAP (ferric reducing antioxidant power) were measured in plasma and urine, and TBARS, GSH/GSSG ratio, TAC and FRAP in saliva, using standard spectrophotometric and fluorometric methods. Salivary GSH/GSSG and urinary AOPP were higher in females. Urinary fructosamine, GSH/GSSG and FRAP were higher in males. Urinary TAC and FRAP negatively correlated with age, and urinary GSH/GSSG positively correlated with weight. We determined that urine and saliva can be obtained non-invasively from mice, in sufficient amounts for reliable oxidative status assessment. Further studies are needed to uncover whether these biofluids reflect systemic oxidative status in diseases.

The Large Effect Size of Urinary Total Antioxidant Capacity in Behavioral Symptoms of Young Autistic Individuals: Comparion with Omega-3 Fatty Acid and Superoxide Dismutase in Plasma

Objective: The imbalance between increased oxidative stress and reduced antioxidant defense has been implicated in the pathophysiology of autism spectrum disorders (ASD). Which of these has a greater impact on ASD behavioral symptoms is still unclear. We measured urinary levels of the oxidative stress biomarker hexanoyl-lysine (HEL), the total antioxidant capacity (TAC) and the DNA methylation biomarker 8-hydroxy-2′-deoxyguanosine (8- OHdG) and their relation to the plasma levels of the oxidative stress biomarker superoxide dismutase (SOD) and of the anti-inflammatory fatty acid eicosapentaenoic acid (EPA). Methods: We studied the relationships between these biomarkers and behavioral symptoms in 19 individuals with ASD (mean age 10.9 ± 5.3 years) and 11 healthy controls (mean age 14.3 ± 6.3 years). Behavioral symptoms were evaluated using the Aberrant Behavior Checklist (ABC). Results: Ages were not significant difference between two groups. The ASD group showed significantly reduced levels of urinary TAC and significantly increased levels of urinary HEL compared to the control group. Urinary 8- OHdG levels or plasma SOD and EPA levels were not significantly different between the two groups. The ABC subscale and total scores were significantly higher in the ASD group had significantly higher ABC subscale and total scores than he control group. Stepwise regression analysis and the standardized regression coefficient indicated that urinary TAC levels provided greater impact for distinguishing the two groups. There was significant correlation between the urinary TAC levels and plasma EPA levels and the ABC irritability scores. Conclusion: Urinary TAP levels may be important in the imbalance between the urinary levels of HEL and TAC, and altered plasma SOD levels may contribute to this imbalance.

Preventing, treating, and predicting barbering: A fundamental role for biomarkers of oxidative stress in a mouse model of Trichotillomania.

Barbering, where a “barber” mouse plucks hair from its cagemates or itself, is both a spontaneously occurring abnormal behavior in mice and a well validated model of Trichotillomania (TTM). N-Acetylcysteine, (NAC) a cysteine derived food additive, is remarkably effective in treating TTM patients, but its mechanism of action is unknown. Reactive Oxygen Species (ROS), also known as free radicals, form as a natural byproduct of the normal metabolism of oxygen. Under normal circumstances, cells are able to defend themselves against ROS damage with antioxidant pathways. NAC is the precursor to the main antioxidant produced to defend the brain. Therefore, we hypothesized that barbering is a disease of oxidative stress, whereby ROS and/or a failure of antioxidant defenses leads to neuronal damage that induces barbering in susceptible animals. We tested this hypothesis in 32 female C57BL/6J mice by treating half with 1g/kg BW/day of NAC in their diet, and testing for protection against developing barbering behavior and curing of barbering behavior, and simultaneously testing for a panel of biomarkers of oxidative stress. NAC reduced the chance that mice would be barbers, and this effect did not differ between healthy (i.e. prevention) and affected animals (i.e. cure). Barbering animals had elevated urinary antioxidant capacity, indicative of oxidative stress, at all timepoints. Additionally, after treatment the risk of barbering increased with decreasing hydroxy-2′-deoxyguanosine (8-OHdG) levels, and with increasing glutathione (GSH) and oxidized glutathione (GSSG) levels, further indicating that barbering mice were under oxidative stress regardless of treatment with NAC. We did not find compelling evidence that urinary total antioxidant capacity, or urinary 8-OHdG, could predict response to NAC treatment. We conclude that NAC is effective in preventing and/or curing barbering at least in part by promoting GSH synthesis, thereby preventing oxidative damage.

The effect of sunblock against oxidative stress in farmers: a pilot study.

Farmers are frequently exposed to ultraviolet (UV) radiation which causes various diseases by inducing oxidative stress. This study aimed to assess the effects of sunblock on oxidative stress in the body. Eighty-seven farmers were divided into two groups: those who wore sunblock for five days and those who did not. The total antioxidant capacity (TAC) in urine, which is an antioxidant indicator, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in urine, an oxidative stress indicator, were measured. The urinary TAC of sunblock users was significantly higher than that of non-users, but urinary 8-OHdG levels were not significantly different. Even after adjustment for potential confounders, urinary TAC was found to be markedly increased with sunblock usage. These results suggest that sunblock is effective in preventing oxidative stress among farmers. In addition, they show that urinary TAC can be used as a good effect marker of oxidative stress caused by UV exposure.

Salivary and Urinary Total Antioxidant Capacity as Biomarkers of Oxidative Stress in Humans.

Total Antioxidant Capacity (TAC) is a biomarker often used in order to investigate oxidative stress in many pathological conditions. Saliva and urine can be collected noninvasively and represent attractive diagnostic fluids for detecting biomarkers of various pathological conditions. The reviewed case-control and intervention studies that measured salivary or urinary TAC revealed that diseases, antioxidant foods, or supplements and age, gender, and lifestyle factors influenced salivary or urinary TAC. Salivary and urinary TAC were particularly affected by oral or renal status, respectively, as well as by infection; therefore these factors must be taken into account in both case-control and intervention studies. Furthermore, some considerations on sample collection and normalization strategies could be made. In particular, unstimulated saliva could be the better approach to measure salivary TAC, whereas 24 h or spontaneous urine collection should be chosen on the basis of the study outcome and of the creatinine clearance. Finally, the uric acid-independent TAC could be the better approach to evaluate red-ox status of body, in particular after nutritional interventions and in diseases associated with hyperuricaemia.

Urinary 8-hydroxy-2′-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection

Background: There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI).Methods: Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2′-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement.Results: Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings.Conclusions: High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Antioxidant Signal and Kidney Injury Molecule-1 Levels in Shockwave Lithotripsy Induced Kidney Injury

Shockwave lithotripsy (SWL) induces acute kidney injury (AKI) that extends from the papilla to the outer cortex by causing ischemia and the production of nephrotoxic agents. Direct ischemic damage and the generation of free radicals cause injury to the proximal tubular cells. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is upregulated in proximal tubular cells after ischemic or nephrotoxic injury and is not expressed in healthy kidneys. We evaluated the extent of free radical production in response to SWL by measuring urinary total antioxidant capacity (TAC) and total oxidant status (TOS). Furthermore, we investigated the severity of SWL-induced kidney injury by measuring KIM-1 expression levels. The study population comprised 30 patients who were carefully selected and 30 age and sex matched control subjects. All patients received the same SWL procedure. Midstream urine samples were collected from patients before SWL and at 120 minutes after SWL. Urine KIM-1 levels were measured by enzyme-linked immunosorbent assay, and TAC and TOS were measured via spectrophotometry. Mean levels of TAC (2.88±0.56 mmolTxEq/L),TOS (8.27±1.57 μmolH2O2Eq/L), and KIM-1 (0.55±0.08 ng/mL) before SWL were not significantly different from mean TAC, TOS, and KIM-1 levels measured from the control group at 2.81±0.42 mmolTxEq/L, 10.73±1.4 μmolH2O2Eq/L, and 0.51±0.07 ng/mL, respectively. Two hours after SWL, mean urine TAC levels (2.81±0.85 mmolTxEq/L, P=0.02) were decreased and mean KIM-1 expression (0.85±0.11 ng/mL, P=0.01) was significantly increased, but there was no significant difference in mean TOS levels (11.24±1.9 μmolH2O2Eq/L, P=0.627) compared with the control group. The increased burden of free radical oxidants in the setting of decreasing antioxidant capacity may be one of the initial indicators of AKI after SWL. Moreover, KIM-1 demonstrates great potential as an early and noninvasive biomarker of SWL-induced kidney injury.

Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans

Melatonin and serotonin rhythms, which exhibit a close association with the endogenous circadian component of sleep, are attenuated with increasing age. This decrease seems to be linked to sleep alterations in the elderly. Chrononutrition is a field of chronobiology that establishes the principle of consuming foodstuffs at times of the day when they are more useful for health, improving, therefore, biorhythms and physical performance. Our aim was to analyze whether the consumption of cereals enriched with tryptophan, the precursor of both serotonin and melatonin, may help in the reconsolidation of the sleep/wake cycle and counteract depression and anxiety in 35 middle-aged/elderly (aged 55-75 year) volunteers in a simple blind assay. Data were collected for 3 weeks according to the following schedule: The control week participants consumed standard cereals (22.5 mg tryptophan in 30 g cereals per dose) at breakfast and dinner; for the treatment week, cereals enriched with a higher dose of tryptophan (60 mg tryptophan in 30 g cereals per dose) were eaten at both breakfast and dinner; the posttreatment week volunteers consumed their usual diet. Each participant wore a wrist actimeter that logged activity during the whole experiment. Urine was collected to analyze melatonin and serotonin urinary metabolites and to measure total antioxidant capacity. The consumption of cereals containing the higher dose in tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency. Urinary 6-sulfatoxymelatonin, 5-hydroxyindoleacetic acid levels, and urinary total antioxidant capacity also increased respectively after tryptophan-enriched cereal ingestion as well as improving anxiety and depression symptoms. Cereals enriched with tryptophan may be useful as a chrononutrition tool for alterations in the sleep/wake cycle due to age.

Effect of ingestion of dark chocolates with similar lipid composition and different cocoa content on antioxidant and lipid status in healthy humans

The association between in vitro antioxidant capacity of dark chocolates with different cocoa percentage and the in vivo response on antioxidant status was investigated. In a randomized crossover design, 15 healthy volunteer consumed 100g of high antioxidants dark chocolate (HADC) or dark chocolate (DC). In vitro, HADC displayed a higher Total Antioxidant Capacity (TAC) than DC. In vivo, plasma TAC significantly peaked 2h after ingestion of both chocolates. TAC levels went back to zero 5h after DC ingestion whilst levels remained significantly higher for HADC. HADC induced a significantly higher urinary TAC in the 5–12h interval time than DC. No change was detected in urinary excretion of F2-isoprostanes. Plasma thiols and triacylglycerol (TG) levels significantly increased for both chocolate with a peak at 2h remaining significantly higher for DC after 5h respect to HADC. Results provide evidence of a direct association between antioxidant content of chocolate and the extent of in vivo response on plasma antioxidant capacity.

High endogenous melatonin concentrations enhance sperm quality and short‐term in vitro exposure to melatonin improves aspects of sperm motility

Although human seminal fluid contains melatonin and spermatozoa reportedly possess membrane melatonin receptors, there are no experimental studies that have ascertained the relationship between melatonin and male infertility. This study evaluated whether urinary 6-sulfatoxymelatonin and urinary total antioxidant capacity correlate with different seminal parameters including sperm concentration, motility and morphology. Also, the in vitro effects of melatonin on human sperm motility were investigated. Semen samples from 52 men who were counselled for infertility were obtained. Sperm concentration was determined using the haemocytometer method, motility kinematic parameters were assessed using a computer-aided semen analysis system, while morphology and vitality were evaluated after Diff-Quick and Eosin-Nigrosin vital staining, respectively. For the quantification of urinary 6-sulfatoxymelatonin, a commercial ELISA kit was used, and urinary total antioxidant capacity was evaluated by means of a colorimetric assay kit. For the in vitro effects of melatonin, samples were incubated for 30min in the presence or absence of 1mm melatonin. Both urinary 6-sulfatoxymelatonin and total antioxidant capacity levels positively correlated with sperm concentration, motility and morphology, as well as negatively correlated with the number of round cells. Additionally, 30-min exposure of sperm to 1mm melatonin improved the percentage of motile and progressively motile cells and decreased the number of static cells, thereby promoting the proportion of rapid cells. Therefore, melatonin improves semen quality, which is important because melatonin supplementation may be potentially used to obtain a successful assisted reproductive technique outcome.

Jerte Valley Cherry-Enriched Diets Improve Nocturnal Rest and Increase 6-Sulfatoxymelatonin and Total Antioxidant Capacity in the Urine of Middle-Aged and Elderly Humans

Tryptophan, serotonin, and melatonin, present in Jerte Valley cherries, participate in sleep regulation and exhibit antioxidant properties. The effect of the intake of seven different Jerte Valley cherry cultivars on the sleep-wake cycle, 6-sulfatoxymelatonin levels, and urinary total antioxidant capacity in middle-aged and elderly participants was evaluated. Volunteers were subjected to actigraphic monitoring to record and display the temporal patterns of their nocturnal activity and rest. 6-sulfatoxymelatonin and total antioxidant capacity were quantified by enzyme-linked immunosorbent assay and colorimetric assay kits, respectively. The intake of each of the cherry cultivars produced beneficial effects on actual sleep time, total nocturnal activity, assumed sleep, and immobility. Also, there were significant increases in 6-sulfatoxymelatonin levels and total antioxidant capacity in urine after the intake of each cultivar. These findings suggested that the intake of Jerte Valley cherries exerted positive effect on sleep and may be seen as a potential nutraceutical tool to counteract oxidation.

Urinary excretion of 3,N4-etheno-2'-deoxycytidine in humans as a biomarker of oxidative stress: association with cigarette smoking.

Smokers are known to have elevated levels of lipid peroxidation, a form of oxidative stress. Etheno DNA adduct formation can originate from endogenous lipid peroxidation or from exogenous exposure of carcinogens. Using a modified stable isotope dilution GC/negative ion chemical ionization/MS assay originally developed for urinary 3,N(4)-ethenocytosine (epsilonCyt), the nucleoside 3,N(4)-etheno-2'-deoxycytidine (epsilondCyd) was detected for the first time in human urine. The presence of epsilondCyd in human urine was confirmed by LC/electrospray ionization/tandem MS. Concentrations of epsilondCyd in the 24 h urine samples from healthy individuals not occupationally exposed to industrial chemicals were in the range between 0 and 0.80 nM. A statistically significant correlation was established between cigarette smoking and urinary excretion of epsilondCyd after being adjusted for creatinine (p = 0.004). Furthermore, the urinary total antioxidant capacity was found to correlate inversely with the epsilondCyd levels (r = -0.50, p = 0.02). The results indicate that urinary epsilondCyd may provide a valuable noninvasive biomarker for oxidative DNA damage.