Oxidative Stress-related Biomarkers Research Articles

Urinary paraben concentrations among pregnant women and their matching newborn infants of Korea, and the association with oxidative stress biomarkers

Parabens have been used in multiple products including personal care products, pharmaceuticals, and foods for more than 50years but increasing numbers of studies have raised concerns on their safety. The present study was designed to determine urinary paraben levels among pregnant women and their matching newborn infants (<48h after delivery), and the association between paraben levels and stress markers. Pregnant women (n=46) and their matching newborn infants were recruited from four university hospitals located in Seoul, Ansan and Jeju of Korea, 2011. Parabens including methyl paraben (MP), ethyl paraben (EP), n-propyl paraben (PP), and n-butyl paraben (BP) were measured in the urine using an automatic, high throughput online SPE–LC–MS/MS method. Urinary concentrations were normalized with specific gravity (SG). Free cortisol, malondealdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in the urine as stress marker. Urinary MP was detected as the highest, and BP was detected as the lowest paraben in the urine samples of both pregnant women and their infants. Significant correlations between paraben concentrations of maternal and their newborn infant's urine were observed. The levels of urinary parabens among Korean pregnant women are comparable to those reported elsewhere, except for EP which were 4–9 folds higher than pregnant women of other countries. The ratios of infant to maternal urinary paraben concentrations varied between 0.5 and 0.6 for MP and PP, but approximately 10 fold lower for EP. Urinary MP or EP levels were associated with several oxidative stress related biomarkers such as urinary 8-OHdG and MDA, even after the adjustment of relevant covariates such as maternal age, mode of delivery, pre-pregnancy BMI, gestational age and parity. This is the first study that reported the levels of major parabens in the first urine of newborn infants. Further studies are warranted to understand the implications of paraben exposure among biologically susceptible human populations.

The protective effects of selenium on cadmium-induced oxidative stress and apoptosis via mitochondria pathway in mice kidney

Selenium, an essential trace element, showed the significant protective effects against kidney damage induced by some heavy metals. Our previous research have found that the protection effects of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium (Cd)-induced LLC-PK1 cells. The present study as a continuation of our earlier one to investigate the protective effects and mechanism of selenium on Cd-induced apoptosis of kidney in vivo. Cadmium exposure increased the production of reactive oxygen species (ROS) and altered the levels of oxidative stress related biomarkers in kidney tissue. A concomitant by the loss of mitochondrial membrane potential, cytochrome c release and regulation of VDAC, Bcl-2 and Bax were observed. Apoptotic nature of cell death is confirmed by activation of caspase-3, which is also supported by histological examination. During the process, selenium played a beneficial role against Cd-induced renal damage. Pretreatment with selenium partially blocked Cd-induced ROS generation, inhibited Cd induced mitochondrial membrane potential collapse, prevented cytochrome c release, inhibited caspase activation and changed the level of VDAC, Bcl-2 and Bax. Combining all, results suggest that selenium has an ability to inhibit mitochondrial apoptotic pathway in oxidative stress mediated kidney dysfunction caused by cadmium.

A review of the "Omics" approach to biomarkers of oxidative stress in Oryza sativa.

Physiological and ecological constraints that cause the slow growth and depleted production of crops have raised a major concern in the agriculture industry as they represent a possible threat of short food supply in the future. The key feature that regulates the stress signaling pathway is always related to the reactive oxygen species (ROS). The accumulation of ROS in plant cells would leave traces of biomarkers at the genome, proteome, and metabolome levels, which could be identified with the recent technological breakthrough coupled with improved performance of bioinformatics. This review highlights the recent breakthrough in molecular strategies (comprising transcriptomics, proteomics, and metabolomics) in identifying oxidative stress biomarkers and the arising opportunities and obstacles observed in research on biomarkers in rice. The major issue in incorporating bioinformatics to validate the biomarkers from different omic platforms for the use of rice-breeding programs is also discussed. The development of powerful techniques for identification of oxidative stress-related biomarkers and the integration of data from different disciplines shed light on the oxidative response pathways in plants.

Protective role of silymarin against manganese‐induced nephrotoxicity and oxidative stress in rat

Metal toxicity may occur after exposure from many sources. Oxidative stress is thought to be involved in manganese-induced toxicity and leads to various health disorders. Silymarin (SIL), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to assess the toxicity of manganese (Mn) on oxidative stress and DNA damage in the kidney of rats and its alleviation by SIL. Manganese was given orally in drinking water (20 mg MnCl2 /mL) with or without SIL administration (100 mg /kg intraperitoneally) for 30 days. Our data showed that SIL significantly prevented Mn induced nephrotoxicity, indicated by both diagnostic indicators of kidney injury like plasma urea, uric acid and creatinine and urinary electrolyte levels and by histopathological analysis. Moreover, Mn-induced profound elevation of the production of reactive oxygen species (ROS) and altered the levels of oxidative stress related biomarkers in kidney tissue. This is evidenced by the increase of lipid peroxidation, protein carbonylation, DNA fragmentation and urinary hydrogen peroxide, while, the activities of enzymatic antioxidant and glutathione level were decreased. Treatment with SIL reduced the alterations in the renal and urine markers, decreasing lipid peroxidation markers, increasing the antioxidant cascade and decreasing the Mn-induced damage. All these changes were supported by histopathological observations. These findings suggested that the inhibition of Mn-induced damage by SIL was due at least in part to its antioxidant activity and its capacity to modulate the oxidative damage.

Oxidative stress-related biomarkers in essential hypertension and ischemia-reperfusion myocardial damage.

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, with hypertension being a major risk factor. Numerous studies support the contribution of reactive oxygen and nitrogen species in the pathogenesis of hypertension, as well as other pathologies associated with ischemia/reperfusion. However, the validation of oxidative stress-related biomarkers in these settings is still lacking and novel association of these biomarkers and other biomarkers such as endothelial progenitor cells, endothelial microparticles, and ischemia modified albumin, is just emerging. Oxidative stress has been suggested as a pathogenic factor and therapeutic target in early stages of essential hypertension. Systolic and diastolic blood pressure correlated positively with plasma F2-isoprostane levels and negatively with total antioxidant capacity of plasma in hypertensive and normotensive patients. Cardiac surgery with extracorporeal circulation causes an ischemia/reperfusion event associated with increased lipid peroxidation and protein carbonylation, two biomarkers associated with oxidative damage of cardiac tissue. An enhancement of the antioxidant defense system should contribute to ameliorating functional and structural abnormalities derived from this metabolic impairment. However, data have to be validated with the analysis of the appropriate oxidative stress and/or nitrosative stress biomarkers.

Single-wall carbon nanotube-induced airway hyperresponsiveness in rats and a postulated mechanism of action

Inflammatory responses, oxidative stress, as well as fibrosis in lungs induced by a type of nano-sized carbon nanotubes (single-walled carbon nanotubes (SWCNTs)) have been investigated. However, studies examining the effects of SWCNTs on airway hyperresponsiveness (AHR) are not so numerous. We examined the effects of pulmonary exposure to SWCNTs on AHR and sought the underlying molecular mechanisms. Wistar rats were divided into four experimental groups and repeatedly administered vehicle or 0.02, 0.20 and 2.00 mg kg−1 body weight SWCNTs through the intratracheal route. We found that 0.20 and 2.00 mg kg−1 body weight SWCNTs in rats caused significant exacerbation of AHR. SWCNTs also amplified the lung protein levels of T helper 2 cytokines, immunoglobulin production in serum, profiles of immune cells in lungs, and levels of oxidative stress-related biomarkers in the airways, and exhibited airway remodelling. These results suggest that SWCNTs can exacerbate AHR in rats by enhancing airway inflammation and pulmonary oxidative stress.

Organic Selenium Supplementation Increases Mercury Excretion and Decreases Oxidative Damage in Long-Term Mercury-Exposed Residents from Wanshan, China

Due to a long history of extensive mercury mining and smelting activities, local residents in Wanshan, China, are suffering from elevated mercury exposure. The objective of the present study was to study the effects of oral supplementation with selenium-enriched yeast in these long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 of them were supplemented with 100 μg of organic selenium daily as selenium-enriched yeast while 50 of them were supplemented with the nonselenium-enriched yeast for 3 months. The effects of selenium supplementation on urinary mercury, selenium, and oxidative stress-related biomarkers including malondialdehyde and 8-hydroxy-2-deoxyguanosine were assessed. This 3-month selenium supplementation trial indicated that organic selenium supplementation could increase mercury excretion and decrease urinary malondialdehyde and 8-hydroxy-2-deoxyguanosine levels in local residents.

Impaired redox signaling and mitochondrial uncoupling contributes vascular inflammation and cardiac dysfunction in type 1 diabetes: Protective role of arjunolic acid

Vascular inflammation and cardiac dysfunction are the leading causes of mortality and morbidity among the diabetic patients. Type 1 diabetic mellitus (T1DM) is associated with increased cardiovascular complications at an early stage of the disease. The purpose of the present study was to explore whether arjunolic acid (AA) plays any protective role against cardiovascular complications in T1DM and if so, what molecular pathways it utilizes for the mechanism of its protective action. Streptozotocin (STZ) was used to induce T1DM in experimental rats. Alteration in plasma lipid profile and release of membrane bound enzymes like LDH (lactate dehydrogenase) and CK (creatine kinase) established the association of hyperlipidemia and cell membrane disintegration with hyperglycemia. Hyperglycemia altered the levels of oxidative stress related biomarkers, decreased the intracellular NAD and ATP concentrations. Hyperglycemia-induced enhanced levels of VEGF, ICAM-1, MCP-1 and IL-6 in the plasma of STZ treated animals indicate vascular inflammation in T1DM. Histological studies and FACS analysis revealed that hyperglycemia caused cell death mostly via the apoptotic pathway. Investigating molecular mechanism, we observed NF-κB and MAPKs (p38 and ERK1/2) activations, mitochondrial membrane depolarization, cytochrome C release, caspase 3 activation and PARP cleavage in apoptotic cell death in the diabetic cardiac tissue. Treatment with AA (20 mg/kg body weight) reduced hyperglycemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Results suggest that AA possesses the potential to be a beneficial therapeutic agent in diabetes and its associated cardiac complications.

Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways

In the modern medicine nano particle has been used as a power tool but recently it has been established that nano particle pathophysiologically affects different organs. Recently, we have investigated the role of copper nano particle in liver dysfunction. In the literature, practically little is known about the nano-copper induced renal dysfunction. We, therefore, conducted the present study as a continuation of our earlier one to investigate the molecular mechanism in nano-copper induced kidney dysfunction. Nano-copper exposure increased the production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and altered the levels of oxidative stress related biomarkers in kidney tissue. Signal transduction mechanism studies showed that nano copper exposure reciprocally regulated Bcl-2 family protein expression, disturbed mitochondrial membrane potential and subsequently helped releasing cytochrome c from mitochondria to cytosol. Apoptotic nature of cell death is confirmed by activation of caspases 3 which is also supported by histological study. In addition, we also observed the activation of Fas, caspase 8 and tBid in kidney tissue in this pathophysiology, suggesting the involvement of extrinsic pathways. Combining all, results suggest that nano copper can trigger both intrinsic and extrinsic apoptotic pathways in oxidative stress mediated kidney dysfunction.

Evaluation of dietary factors in relation to the biomarkers of oxidative stress and inflammation in breast cancer risk

Objective This study was conducted to evaluate blood concentrations of inflammatory cytokines and oxidative stress-related biomarkers as risk factors of breast cancer and to determine the relation between these markers and antioxidant nutrient intake. Methods Study subjects were 134 patients with breast cancer and 149 controls. Total antioxidant capacity and concentrations of 8-isoprostane, 8-hydroxy-2′-deoxyguanosine, interleukin (IL)-1β, IL-6, and IL-8 of blood samples were determined. A food-frequency questionnaire was used to assess nutrient intake. Results Patients with breast cancer had significantly higher blood levels of oxidative stress markers compared with control subjects. Plasma concentrations of IL-1β and IL-6 were significantly higher in patients with breast cancer compared with those of control subjects. In the pooled analysis, total antioxidant capacity was significantly decreased with increasing quartiles of carbohydrate intake but was increased with increasing quartiles of total vitamin A intake and vitamin C intake. In addition, 8-hydroxy-2′-deoxyguanosine concentration was decreased with increasing quartiles of vitamin A and β-carotene. No significant association was found between nutrient intake and cytokine concentrations. Conclusions These results suggest that oxidative stress and inflammation may be associated with the risk of breast cancer. Total vitamin A intake was negatively related to oxidative stresses, possibly modifying the risk of breast cancer.

Acute Exposure to Solar Simulated Ultraviolet Radiation Affects Oxidative Stress-Related Biomarkers in Skin, Liver and Blood of Hairless Mice

The ultraviolet (UV) region of solar radiation is a critical factor in the initiation and development of a number of skin diseases. However, it is not only skin which is directly exposed to solar light that is affected by UV radiation, through low molecular weight mediators, generated upon irradiation, "non-skin" tissues can also be affected. The aim of this study was to examine in detail, the acute effects of UVA and UVB wavebands on hairless mice. Female SKH-1 hairless mice were exposed to a single dose of UVB (200, 800 mJ/cm(2)) or UVA (10, 20 J/cm(2)) using a solar simulator. The effects on haematological parameters, activity and/or expression of antioxidant enzymes, level of glutathione (GSH), markers of oxidative damage (lipid peroxidation and carbonylated proteins) were analysed in erythrocytes, plasma, liver and whole skin homogenates. No macroscopic changes were observed either 4 or 24 h after UVA/UVB exposure. The blood count showed a significant increase in leukocyte number and reduction of platelets 4 h following UVA and UVB irradiation, which disappeared 24 h after irradiation except for the higher UVA dose. Changes in oxidative stress-related parameters, particularly activity of catalase (CAT) and superoxide dismutase (SOD) and level of GSH and lipid peroxidation products, were found in skin, erythrocytes and liver. The expression of several enzymes (CAT, SOD, glutathione transferase (GST), nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (NQO1) and hem oxygenase-1 (HO-1)) in skin was affected following UVA and UVB radiation. Increase in carbonylated proteins was found in plasma and skin samples.

Exposure of brown trout ( Salmo trutta L.) to tunnel wash water runoff — Chemical characterisation and biological impact

Washing and cleaning of road tunnels are a routinely performed maintenance task, which generate significant amount of polluted wash-water runoff that normally is discharged to the nearest recipient. The present study was designed to quantify chemical contaminants (trace metals, hydrocarbons, PAH and detergents) in such wash water and assess the short term impact on brown trout ( Salmo trutta L.) based on in situ experiments. Selected endpoints were accumulation of trace metals in gills, haematological variables and hepatic mRNA transcription of five biomarkers reflecting defence against free radicals, trace metals, planar aromatic hydrocarbons and endocrine disruptions which were measured prior (− 3 h), during (1 and 3 h) and after the tunnel wash (14, 38 and 86 h). Our findings showed that the runoff water was highly polluted, but most of the contaminants were associated with particles which are normally considered biologically inert. In addition, high concentrations of calcium and dissolved organic carbon were identified in the wash water, thus reducing metal toxicity. However, compared to the control fish, a rapid accumulation of trace metals in gills was observed. This was immediately followed by a modest change in blood ions and glucose in exposed fish shortly after the exposure start. However, after 38–86 h post wash, gill metal concentrations, plasma ions and glucose levels recovered back to control levels. In contrast, the mRNA transcription of the CYP1A and the oxidative stress related biomarkers TRX and GCS did not increase until 14 h after the exposure start and this increase was still apparent when the experiment was terminated 86 h after the beginning of the tunnel wash. The triggering of the defence systems seemed to have successfully restored homeostasis of the physiological variables measured, but the fish still used energy for detoxification four days after the episode, measured as increased biomarker synthesis.

Repeated pulmonary exposure to single-walled carbon nanotubes exacerbates allergic inflammation of the airway: Possible role of oxidative stress

The development of nanotechnology has increased the risk of environmental exposure to types of particles other than those derived from combustion, namely, industrial nanomaterials. Patients with bronchial asthma are sensitive to inhaled substances, including particulate matter. This study examined the effects of pulmonary exposure to a type of nano-sized carbon nanotube (single-walled nanotubes (SWCNT)) on allergic airway inflammation and sought their cellular mechanisms. In the in vivo experiments, ICR mice were divided into four experimental groups that were repeatedly administered vehicle, SWCNT (50 microg/animal), ovalbumin (OVA; an allergen), or OVA + SWCNT through an intratracheal route and thereafter assayed. SWCNT aggravated allergen-induced pulmonary inflammation with mucus hyperplasia. SWCNT with allergen amplified lung protein levels of T helper (Th) cytokines and chemokines related to allergy and exhibited adjuvant activity for allergen-specific IgG(1) (and IgE) compared with allergen alone. SWCNT accentuated the level/activity of oxidative stress-related biomarkers in the airways in the presence of allergen. In vitro, SWCNT can partially promote/strengthen the maturation/activation/function of bone marrow-derived dendritic cells (DC). Together, these results suggest that SWCNT can exacerbate murine allergic airway inflammation via enhanced activation of Th immunity and increased oxidative stress. In addition, this exacerbation may be partly through the inappropriate activation of antigen-presenting cells, including DC.

Relationship between oxidative stress‐related biomarkers and antioxidant status with asthma and atopy in young adults: a population‐based study

Enhanced oxidative stress has been described in adults who suffer from symptoms of asthma and poor lung function. This study assessed the relation between markers of oxidative stress and antioxidant status and lung function, symptoms of asthma, atopy and bronchial hyperresponsiveness (BHR) in young adults. A sub-sample of 589 individuals aged 22-28 years, selected from a total of 1232 included in a survey assessing early and current risk factors for chronic diseases, participated in the study. Participants were from an agricultural area of Chile, responded to a Spanish version of the European Community Respiratory Health Survey questionnaire, were skin tested to eight allergens, and challenged with methacholine to assess BHR. Five hundred and eighty-five individuals had measures of plasma biomarkers ferric reducing ability of plasma, uric acid, protein carbonyls and 564 had 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) assessed. All participants had detectable plasma 8-iso-PGF(2alpha) and carbonyl levels. There was no indication for an association between markers of antioxidant status or oxidative stress with any of the outcomes studied. The levels of oxidative stress-related biomarkers and antioxidant status in plasma may not be related to asthma in the general population in the absence of more severe symptoms or exacerbations.

Inhibition of nitric oxide synthase promotes facial axonal regeneration following neurorrhaphy

Reconnection of interrupted peripheral nerve by microsurgical suture is a common clinical practice. However, the extent to which peripheral neurorrhaphy improves nerve regeneration and functional recovery remains unsatisfactory. Here, we used anatomical and electrophysiological techniques to investigate the temporal correlation between the expressions of oxidative stress-related biomarkers such as neuronal nitric oxide synthase (nNOS) and the facial axonal regeneration after an immediate facial nerve repair in adult rats since peripheral nerve lesion is well known to induce a dramatic increase of NOS expression in the affected neuronal cell bodies. We found that compared to nerve cut without suture, facial nerve repair not only caused the facial axonal regeneration but also consistently prevented the fluctuations of expressions of oxidative stress-related biomarkers in 10 weeks postlesion. To further elucidate the role of nitric oxide (NO) in the axonal degeneration/regeneration, four different NOS inhibitors were applied to additional rats after facial nerve cut or repair. Both of facial nerve cut + NOS inhibition and facial nerve repair + NOS inhibition were seen to prevent the alterations of expressions of the biomarkers, no matter which NOS inhibitor was used. Moreover, we found that facial nerve repair + NOS inhibition promoted earlier and better axonal regeneration than facial nerve repair, demonstrated by labeling of neuromuscular junctions, retrograde tracing, and electromyography. These results provide direct evidence that peripheral nerve suture and/or treatment of NOS inhibitors can maintain the homeostasis of oxidative stress-related biomarkers, especially nNOS in neuronal cell bodies. These actions may thus facilitate the axonal regeneration.

Abstract B87: A study of tobacco exposure and oxidative stress related biomarkers in oral cancer

Abstract B87 Objective Oral cancer is the leading malignancy in India, with tobacco playing a major role in the etiology. The aims of the present study was (i) to assess tobacco exposure related biomarkers in controls, patients with oral precancers (OPC) and oral cancer patients, (ii) evaluate nitric oxide [as NO2+NO3] and antioxidant enzymes in the subjects and (iii) to evaluate correlation between tobacco exposure and oxidative stress related biomarkers in oral cancer patients. Materials and Methods Healthy individuals (n=90) were grouped into without habit of tobacco (NHT, n=30) and healthy individuals with habit of tobacco (WHT, n=60). Oral cancer patients with a tobacco habit were classified into abstinence (n=62) and non-abstinence (n=64) groups according to status of tobacco habits at the study time. Urinary nicotine and cotinine levels were analyzed by HPLC using a UV detector. Plasma NO2+NO3, superoxide dismutase (SOD) and catalase levels were estimated by spectrophotometry. Results The Odds Ratio (OR) analysis indicated positive associations of both smoking and chewing habits of tobacco with high risk of development of oral cancer. Urinary nicotine and cotinine were significantly elevated in WHT, patients with OPC and oral cancer patients as compared with the NHT group. Levels of urinary nicotine and cotinine were also higher in the non-abstinence group with oral cancers than abstinence group. Mean plasma NO2+NO3 levels were elevated in patients with OPC and oral cancer patients as compared to the controls. Erythrocyte SOD and catalase levels were higher in WHT and patients with OPC as compared to NHT. The erythrocyte SOD and catalase activities were lower in oral cancer patients than patients with OPC. Person’s correlation analysis revealed that the changes in erythrocyte SOD and catalase activities were positively associated with urinary nicotine values. The alterations in plasma NO2+NO3 levels were negatively associated with changes in erythrocyte SOD activities. Conclusion The results confirmed that (i) tobacco chewing and smoking habits are prominent risk factors for development of oral cancer in the western part of India (Gujarat). (ii)Urinary nicotine and cotinine levels can be helpful for screening programs for oral cancer. (iii) The alterations in antioxidant activities were associated with production of nitric oxide in oral cancer, which may have significant role in oral carcinogenesis. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B87.

Evaluation of sex specificity on oxidative stress induced in lungs of mice irradiated by 12C 6+ ions

The aim of this work is to identify if there is sex specificity on 12C 6+ ion-induced oxidative damage in mouse lung at different time points. Kun-Ming mice were divided into two groups, each composed of six males and six females: control group and irradiation group with a single acute dose of 4 Gy. Animals were sacrificed at 2, 4 and 12 h respectively, there lungs were removed immediately, and the oxidative stress-related biomarkers were measured by Diagnostic Reagent Kits. The results showed that the relative activities of superoxide dismutase (4 h), catalase (2 h) and Se-dependent glutathione peroxidase (12 h) have significant changes ( P<0.05) between male groups and female groups, suggesting that the lungs of male mice are more sensitive to counteracting the oxidative challenge. Moreover, higher levels of malondiadehyde and lower contents of glutathione were also found in males, indicating that oxidative stress induced by 12C 6+ ion is pronounced in the lungs of males. We thought that these sex-responded differences may be attributed to the influence of sex hormones.