8-Hydroxy-2'-deoxyguanosine and malondialdehyde in plasma and their association with disease severity in 20 cats with chronic kidney disease.

OBJECTIVES: Oxidative stress is associated with the development and progression of chronic kidney disease (CKD) in humans. The aim of this study was to evaluate the concentrations of oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), in the plasma and urine of cats with different stages of CKD. METHODS: Plasma and urine samples were collected from cats with CKD that were referred to the Veterinary Medical Center of the University of Tokyo between April 2019 and October 2022. Plasma and urine samples were collected from healthy cats (n = 6 at most), cats with stage 2 CKD (n = 8) and stage 3-4 CKD (n = 12), and cats with idiopathic cystitis (disease control, n = 5). Plasma and urine concentrations of 8-OHdG and MDA were measured using ELISA and thiobarbituric acid reactive substances assay kits, respectively. RESULTS: The median plasma 8-OHdG concentrations were 0.156 ng/ml (<0.125-0.210 ng/ml) in the healthy group, <0.125 ng/ml (range <0.125 ng/ml) in the idiopathic cystitis group, 0.246 ng/ml (range 0.170-0.403 ng/ml) in cats with stage 2 CKD and 0.433 ng/ml (range 0.209-1.052 ng/ml) in cats with stage 3-4 CKD. Concentrations in stage 3-4 CKD were significantly higher than those in the healthy and disease control groups. Plasma MDA concentrations were low in the healthy and disease control groups and significantly higher in cats with stage 3-4 CKD. In every cat with CKD, plasma 8-OHdG and MDA concentrations were positively correlated with plasma creatinine concentrations (8-OHdG, rs = 0.68; MDA, rs = 0.67). Urinary 8-OHdG/urinary creatinine (u-CRE) and urinary MDA/u-CRE levels did not differ significantly between the groups; however, it was difficult to evaluate them because of the small sample size. CONCLUSIONS AND RELEVANCE: This report shows that plasma 8-OHdG and MDA concentrations increase with the severity of feline CKD. These markers may be useful for assessing oxidative stress in cats with CKD.

Passive smoking and urinary oxidative biomarkers: A pilot study of healthy travelers from Los Angeles to Beijing.

There is a great heterogeneity in smoking prevalence and tobacco control policy across different countries. However, it is unknown whether this heterogeneity could cause increased passive smoking and adverse health effects among international travelers. In this pilot study, we collected 190 urine samples from 26 Los Angeles residents before (LA-before), during (Beijing), and after (LA-after) a 10-week visit to Beijing to measure biomarkers of passive smoking (cotinine), exposure to polycyclic aromatic hydrocarbons (OH-PAHs), and oxidative stress (malondialdehyde, 8-isoprostane, and uric acid). The geometric mean concentrations of urinary cotinine were 0.14, 1.52, and 0.22 µg/g creatinine in LA-before, Beijing, and LA-after, respectively. Likewise, OH-PAH levels were significantly higher in Beijing as compared to LA-before or LA-after, in association with the urinary cotinine levels. One-fold increase in urinary cotinine levels was associated with 10.1% (95% CI: 5.53-14.8%), 8.75% (95% CI: 2.33-15.6%), and 25.4% (95%CI: 13.1-39.1%) increases in urinary levels of malondialdehyde, 8-isoprotane, and uric acid, respectively. OH-PAHs mediated 9.1-23.3% of the pro-oxidative effects associated with passive smoking. Taken together, our findings indicate that traveling to a city with higher smoking prevalence may increase passive smoking exposure, in association with pro-oxidative effects partially mediated by PAHs.

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice.

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg-1∙d-1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg-1∙d-1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

Health effect research on Hebei Spirit Oil Spill (HEROS) in Korea: a cohort profile.

PURPOSE: The Hebei Spirit Oil Spill occurred on 7 December 2007 and resulted in the spillage of 12 547 kl of crude oil on the coastline near Taean. Historically, this was the largest oil spill in Korean water. The health effect research on Hebei Spirit Oil Spill (HEROS) is a prospective cohort study that aimed to evaluate the long-term health effects of oil spill exposure on residents in the affected community. PARTICIPANTS: The Taean Environmental Health Center initially enrolled adults, adolescents and children living in Taean in 2009 and 2010. Follow-up surveys of participating adults and children were conducted every other year. By 2017, a total of 9585 adults and 2216 children and adolescents were enrolled. Of these, 294 adults and 102 children and adolescents were included in all subsequent surveys. FINDINGS TO DATE: Children who lived closer to the oil spill site exhibited a lower level of pulmonary function and higher prevalence of allergic rhinitis, than those who lived further away from the oil spill site. Adults who lived in a highly exposed area or participated in clean-up work had higher urine levels of the oxidative stress biomarkers malondialdehyde and 8-hydroxydeoxyguanosine. Changes in haematological parameters during a 3-year period were observed in residents of both sexes in highly exposed areas, in addition to increases in respiratory diseases and mental health problems in female and male participants, respectively. FUTURE PLANS: The findings of this study will better enable policy makers to develop environmental health policies intended to prevent adverse health effects in residents of communities affected by oil spills, as well as policies regarding the management of future oil accidents. The HEROS study will continue to follow participants in future and will be updated to enable an investigation of long-term health effects.

Effects of reduced exposure to cigarette smoking on changes in biomarkers of potential harm in adult smokers: results of combined analysis of two clinical studies.

Purpose: Nonconventional vapor products (NVP), designed to reduce exposure to cigarette smoke toxicants (CSTs), could cause changes in biomarkers of potential harm (BoPH). Although, NVPs reduced CSTs exposure compared to conventional cigarettes (CC), the changes in the BoPH values varied among the studies. Hence, further information on BoPH using NVPs is needed. Material and methods: The data of two similarly designed studies using a kind of NVP, a noncombustion and nonheating inhaler type of smokeless tobacco product (NCIT) used under 31-day confinement, were pooled, and the differences in 15 BoPH between smokers and nonsmokers at baseline and between the 1 mg tar CC (CC1) group and NCIT group at Day 28/29 were analyzed. Results: At baseline, the levels of eight BoPH (red blood cells, white blood cells, 8-epi-prostaglandin F2α, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, 11-dehydrothromboxane B2, total cholesterol and glucose) were significantly different between smokers and nonsmokers. At Day 28/29, the levels of six BoPH were significantly different between NCIT and CC1 (8-epi-prostaglandin F2α, malondialdehyde, 11-dehydrothromboxane B2: CC1 > NCIT, total bilirubin, low-density lipoprotein cholesterol and total cholesterol: CC1 < NCIT). Conclusions: Reduced exposure to CSTs has favorable effects on BoPH associated with oxidative stress, antioxidant capacity and platelet activation/coagulation but not in lipid metabolism.

Urinary mutagenicity and other biomarkers of occupational smoke exposure of wildland firefighters and oxidative stress.

Background: Wildland firefighters conducting prescribed burns are exposed to a complex mixture of pollutants, requiring an integrated measure of exposure. Objective: We used urinary mutagenicity to assess if systemic exposure to mutagens is higher in firefighters after working at prescribed burns versus after non-burn work days. Other biomarkers of exposure and oxidative stress markers were also measured. Methods: Using a repeated measures study design, we collected urine before, immediately after, and the morning after a work shift on prescribed burn and non-burn work days from 12 healthy subjects, and analyzed for malondialdehyde (MDA), 8-isoprostane, 1-hydroxypyrene (OH-pyrene), and mutagenicity in Salmonella YG1041 +S9. Particulate matter (PM2.5) and carbon monoxide (CO) were measured by personal monitoring. Light-absorbing carbon (LAC) of PM2.5 was measured as a surrogate for black carbon exposure. Linear mixed-effect models were used to assess cross-work shift changes in urinary biomarkers. Results: No significant differences occurred in creatinine-adjusted urinary mutagenicity across the work shift between burn days and non-burn days. Firefighters lighting fires had a non-significant, 1.6-fold increase in urinary mutagenicity for burn versus non-burn day exposures. Positive associations were found between cross-work shift changes in creatinine-adjusted urinary mutagenicity and MDA (p = 0.0010), OH-pyrene (p = 0.0001), and mass absorption efficiency which is the LAC/PM2.5 ratio (p = 0.2245), respectively. No significant effect of day type or work task on cross-work shift changes in MDA or 8-isoprostane was observed. Conclusion: Urinary mutagenicity may serve as a suitable measure of occupational smoke exposures among wildland firefighters, especially among those lighting fires for prescribed burns.

Urinary metals and metal mixtures and oxidative stress biomarkers in an adult population from Spain: The Hortega Study.

INTRODUCTION: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. OBJECTIVES: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8­oxo­7,8­dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. RESULTS: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA. CONCLUSIONS: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation.

Glycine mitigates renal oxidative stress by suppressing Nox4 expression in rats with streptozotocin-induced diabetes.

Glycine exerts renoprotective effects, but the mechanism remains unclear. Glycine is increasingly recognized as a factor that attenuates oxidative stress, a key mechanism underlying diabetic nephropathy. In this study, we investigated the effects of glycine on diabetic renal injury and oxidative stress by adding 1% glycine in the drinking water of rats with streptozotocin-induced diabetes for 20 weeks. Glycine levels decreased in the plasma and kidney homogenates of diabetic rats but were restored by oral glycine administration. In these diabetic rats, glycine attenuated renal damage, as evidenced by the decreased mesangial expansion, tubular interstitial fibrosis, and neutrophil gelatinase-associated lipocalin (NGAL) expression. Glycine also ameliorated the raise in urinary malondialdehyde (MDA) levels and partially restored renal glutathione levels in diabetic rats. Renal levels of the Nox4 mRNA and protein, a major source of renal oxidative stress, were suppressed by the treatment with glycine. Immunohistological analysis revealed that glycine had protective effects on the tubular area rather than the glomerular area. Our results strongly suggest that the protective effect of glycine on renal oxidative stress and structural damage may be linked to enhancement of GSH synthesis and suppression of renal Nox4 expression in diabetic rats.

URINARY MALONDIALDEHYDE AS A PREDICTIVE AND DIAGNOSTIC MARKER FOR NEONATAL ACUTE KIDNEY INJURY.

Newborns are especially prone to oxidative stress (OS). Many free radical-mediated diseases have been described in newborns including bronchopulmonary dysplasia, respiratory distress syndrome, encephalopathy, and kidney injury. Objective of this work was to determine predictive and diagnostic value of urinary malondialdehyde (UMDA) as a marker for acute kidney injury (AKI) in critically sick full-term newborns. 67 critically sick full-term neonates were enrolled in the study including 31 newborns with AKI (group I) and 36 newborns without AKI (group II). The control group included 40 healthy full-term neonates (group III). The level of UMDA was measured by means of the test based on the reaction of MDA to thiobarbituric acid. The mean and 95% confidence interval (CI) for UMDA was 12.7 (11.5; 13.9) µmol/l in group I, 10.2 (9.61; 10.8) µmol/l in group II, 9.01 (8.16; 9.93) µmol/l in group III (pI-II<0.05; pI-III<0.05; pII-III<0.05). ROC curve analysis showed that UMDA had AUC 0.80 (95% CI 0.68; 0.93, p=0.0014) for AKI. The optimum UMDA cut-point was 12.0µmol/l. For AKI sensitivity and specificity of UMDA were determined to be 68.2% (95% CI 45.1; 86.1%) and 85.7% (95% CI 69.7; 95.1%) respectively, with positive predictive value of 75.0% (95% CI 55.9; 87.6%), and negative predictive value of 81.1% (95% CI 69.7; 88.9%), positive likelihood ratio of 4.77 (95% CI 2.02; 11.3), and negative likelihood ratio of 0.37 (95% CI 0.20; 0.69). This data support studies to evaluate UMDA as an immediate biomarker for AKI in critically sick newborns. However, a larger study should be conducted to assess the diagnostic accuracy of other serum and urinary markers for OS and renal dysfunction, which would enable us to formulate a mathematical model for the prognosis and diagnosis of AKI in newborns.

Association between human exposure to heavy metals/metalloid and occurrences of respiratory diseases, lipid peroxidation and DNA damage in Kumasi, Ghana.

Heavy metals and metalloids contamination in soils, water, food and livers of wild rats have been studied in Kumasi, Ghana and despite the estimated risks to residents, there is no epidemiological study to ascertain these projections. In addition, the World Health Organization and International Agency for Research on Cancer have reported an increase in respiratory diseases and cancers, in Ghana. The study's purpose was therefore to explore the potential associations between metal exposure and occurrences of respiratory diseases, lipid peroxidation and/or DNA damage to different age groups and sexes in Kumasi. Human urine was collected from the general population in urban and control sites in Kumasi and nine metals were measured in each sample. Results showed that although Zn was the most abundant total urinary As concentration was higher in 83% of samples compared to reference values. Urinary concentrations of metals, malondialdehyde (MDA) and 8-hydroxy-2-deoxy-guanosine (8-OHdG) were higher in urban sites compared to the control site. Based on the results obtained, there was no significant correlation between urinary metals and age. However, urinary Cd and MDA were highest in age groups 61-85 and 3-20 years, respectively. Significantly higher levels of urinary Co, As and Cd were detected in female participants. The study revealed that exposure to As was significantly associated with increased odds of asthma (odds ratio (OR) = 2.76; CI: 1.11-6.83) and tachycardia (OR = 3.93; CI: 1.01-15.4). Significant association was observed between urinary metals and MDA and 8-OHdG indicating possibility of lipid peroxidation and/or DNA damage in Kumasi residents.

Mammographic density, blood telomere length and lipid peroxidation.

Extensive mammographic density is a strong risk factor for breast cancer, but may also be an indicator of biological age. In this study we examined whether mammographic density is related to blood telomere length, a potential marker of susceptibility to age-related disease. We measured mammographic density by a computer assisted method and blood telomere length using a validated PCR method. Urinary malondialdehyde (MDA), a marker of lipid peroxidation, was measured in 24 hour urine collections. In the 342 women examined telomere length was negatively correlated with age, was lower in postmenopausal compared to premenopausal women and in smokers compared to non-smokers, and was positively correlated with urinary MDA. Telomere length was not associated with percent mammographic density or dense area, before or after adjustment for risk factors and MDA. However, there was a significant interaction between telomere length and MDA in their association with mammographic density. At lower levels of MDA, mammographic density and telomere length were inversely associated; while at high levels of MDA, there was evidence of a J-shaped association between mammographic density and telomere length. Further work is need to replicate these results and to examine the association of mammographic density with age-related chronic disease and mortality.

Blood mercury concentrations are associated with decline in liver function in an elderly population: a panel study.

BACKGROUND: Mercury is a toxic heavy metal and is known to affect many diseases. However, few studies have examined the effects of mercury exposure on liver function in the general population. We examined the association between blood mercury concentrations and liver enzyme levels in the elderly. METHODS: We included 560 elderly participants (60 years or older) who were recruited from 2008 to 2010 and followed up to 2014. Subjects visited a community welfare center and underwent a medical examination and measurement of mercury levels up to five times. Analyses using generalized estimating equations model were performed after adjusting for age, sex, education, overweight, alcohol consumption, smoking, regular exercise, high-density lipoproteins cholesterol, and total calorie intake. Additionally, we estimated interaction effects of alcohol consumption with mercury and mediation effect of oxidative stress in the relationship between mercury levels and liver function. RESULTS: The geometric mean (95% confidence interval (CI)) of blood mercury concentrations was 2.81 µg/L (2.73, 2.89). Significant relationships were observed between blood mercury concentrations and the level of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT), after adjusting for potential confounders (P < 0.05). The odds ratios of having abnormal ALT levels were statistically significant in the highest mercury quartile compared to those with the lowest quartile. Particularly, regular alcohol drinkers showed greater effect estimates of mercury on the liver function than non-drinkers groups. There was no mediation effect of oxidative stress in the relationship between blood mercury concentrations and liver function. CONCLUSIONS: Our results suggest that blood mercury levels are associated with elevated liver enzymes and interact with alcohol consumption for the association in the elderly.

A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among iowa corn farmers.

Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism's antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. We utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40-60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2'-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. We calculated ß estimates and 95% confidence intervals (95%CI) for each pesticide-oxidative stress marker combination using multivariate linear mixed-effect models for repeated measures. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared with controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (ß = 0.066, 95%CI = 0.008-0.124) and 8-isoPGF (ß = 0.088, 95%CI = 0.004-0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases. Environ. Mol. Mutagen. 58:30-38, 2017. © 2016 Wiley Periodicals, Inc.

Markers of lipid oxidative damage in the exhaled breath condensate of nano TiO2 production workers.

Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO2. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C6-C12) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 104 to 2.32 × 104 particles/cm3 with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m3. All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO2 complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.

Urinary oxidative stress biomarkers among local residents measured 6years after the Hebei Spirit oil spill.

In December 2007, the Hebei Spirit oil spill occurred on the west coast of South Korea. Association between crude oil exposure and the levels of urinary oxidative stress biomarkers was reported among the local residents, 1.5years after the accident. The aim of this study was to follow-up possible longer-term effects of the oil spill among the residents near the oil spill. Six years after the accident, urinary oxidative stress biomarkers of the residents were associated with surrogates of oil exposure. The target subjects were divided into two groups based on the distance of their residence to the spill site, i.e., those near the spill site ('Near' group, n=476), and those far from the spill ('Far' group, n=152). A questionnaire was administered by trained interviewers or self-reporting, and demographic information and other parameters of the participants, such as socioeconomic status, smoking and drinking behaviors, disease history, and duration of clean-up activities after the spill, were collected. The participants' levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 12 h urine samples were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. A general linear model was used for statistical analysis. Urinary MDA and 8-OHdG levels measured from 'Near' group, i.e., geometric mean of 2.19µmol/g creatinine, and 5.41µg/g creatinine, respectively, were higher than those of 'Far' group. Especially, urinary 8-OHdG levels in the 'Near' group were significantly higher than those of 'Far' after adjusting relevant covariates. In addition, the duration of clean-up activities showed a significant association with both urinary 8-OHdG and MDA levels. Even 6years after the oil spill, positive associations between oxidative stress biomarkers and surrogates of oil exposure were evident. While the present study design lacks biomarkers of exposure, the results of this study suggest that the consequences of oil pollution may last for years.

Associations between urinary biomarkers of oxidative stress and air pollutants observed in a randomized crossover exposure to steel mill emissions.

The effects of industrial air pollution on human health have not been as thoroughly investigated as those of urban air pollution which originates mostly from automotive transport. To better assess the health impacts of point sources of industrial air pollution, a randomized crossover exposure study was conducted. Sixty one young and healthy volunteers were randomly assigned to spend five consecutive eight-hour days near a steel mill or at a location five kilometres away. After a nine or sixteen-day washout period, volunteers spent another five consecutive days at the second site. Meteorological conditions and air pollutants were monitored at both exposure sites. On each exposure day, the first morning urine was collected along with a second urine sample obtained immediately before leaving the exposure site at the end of the day. Urinary levels of biomarkers of oxidative stress 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage), malondialdehyde (MDA, a biomarker of lipid peroxidation), 8-isoprostane (8-IsoP, a bioactive metabolite resulting from the peroxidation of arachidonic acid) and Vascular Endothelial Growth Factor (VEGF, involved in response to oxidative stress) were measured. According to mixed-effects linear regression models, intra-individual variations in 8-OHdG urinary levels were significantly associated with exposure site, but surprisingly, lower levels were observed at the steel mill site. Delayed, temporally-defined associations with specific air pollutants were observed for 8-OHdG, 8-IsoP and VEGF. However, these associations were subtle, presented complex patterns and their biological consequences remain unclear.

Environmental exposure and effects on health of children from a tobacco-producing region.

Children may be environmentally exposed to several hazards. In order to evaluate the health of children living in a tobacco-producing region, different biomarkers of exposure and effect, as well as hematological parameters, were evaluated. Biomarkers of exposure to the following xenobiotics were assessed: pesticides, nicotine, toxic elements, and organic solvents. Oxidative damage markers malondialdehyde (MDA) and protein carbonyls (PCO), vitamin C, microalbuminuria (mALB) levels, and N-acetyl-ß-D-glucosaminidase (NAG) activity were also evaluated. Peripheral blood samples and urine were collected from 40 children (6-12 years), at two different crop periods: in the beginning of pesticide applications (period 1) and in the leaf harvest (period 2). The Wilcoxon signed-rank test for paired data was used to evaluate the differences between both periods. Biomarkers of exposure cotinine in urine and blood chromium (Cr) levels were increased in period 1 when compared to period 2. Moreover, a significant reduced plasmatic activity of butyrylcholinesterase (BuChE) was observed in period 2 in relation to period 1. Blood Cr levels were above the recommended by WHO in both evaluations. The biomarkers MDA and PCO as well as the kidney dysfunction biomarker, mALB, presented levels significantly increased in period 1. Additionally, decreased lymphocytes and increased basophils were also observed. Cotinine was positively associated with PCO, and Cr was positively associated with PCO and MDA. The increased Cr levels were associated with decreased lymphocytes and increased basophils. Our findings demonstrate that children environmentally exposed to xenobiotics in rural area may present early kidney dysfunction, hematological alterations, as well as lipid and protein damages, associated with co-exposure to different xenobiotics involved in tobacco cultivation.

Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

BACKGROUND: Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. METHODS: Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. RESULTS: Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). CONCLUSION: A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is recommended that additional exposure metrics such as PNC are considered for occupational risk assessments. Our findings highlight the importance of increasing awareness of TIG welding fume toxicity, especially given the realities of welding workplaces that may lack ventilation; and beliefs among interviewed welders that TIG represents a cleaner and safer welding process.

Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China.

Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4µg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7µg/g Cre) and urban (10.9µg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6µg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2µg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4µg/g Cre) and non-smokers (24.7µg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies.

Paracellular epithelial sodium transport maximizes energy efficiency in the kidney.

Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2-null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2-null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency.