Metals and oxidative potential in urban particulate matter influence systemic inflammatory and neural biomarkers: A controlled exposure study.

BACKGROUND: Oxidative stress and inflammation are considered to be important pathways leading to particulate matter (PM)-associated disease. In this exploratory study, we examined the effects of metals and oxidative potential (OP) in urban PM on biomarkers of systemic inflammation, oxidative stress and neural function. METHODS: Fifty-three healthy non-smoking volunteers (mean age 28 years, twenty-eight females) were exposed to coarse (2.5-10 µm, mean 213 µg/m3), fine (0.15-2.5 µm, 238 µg/m3), and/or ultrafine concentrated ambient PM (<0.3 µm, 136 µg/m3). Exposures lasted 130 min, separated by ≥2 weeks. Metal concentrations and OP (measured by ascorbate and glutathione depletion in synthetic airway fluid) in PM were analyzed. Blood and urine samples were collected pre-exposure, and 1-h and 21-h post exposure for assessment of biomarkers. We used mixed-regression models to analyze associations adjusting for PM size and mass concentration. RESULTS: Results for metals were expressed as change (%) from daily pre-exposure biomarker levels after exposure to a metal at a level equivalent to the mean concentration. Exposure to various metals (silver, aluminum, barium, copper, iron, potassium, lithium, nickel, tin, and/or vanadium) was significantly associated with increased levels of various blood or urinary biomarkers. For example, the blood inflammatory marker vascular endothelia growth factor (VEGF) increased 5.3% (95% confidence interval: 0.3%, 10.2%) 1-h post exposure to nickel; the traumatic brain injury marker ubiquitin C-terminal hydrolase L1 (UCHL1) increased 11% (1.2%, 21%) and 14% (0.3%, 29%) 1-h and 21-h post exposure to barium, respectively; and the systemic stress marker cortisol increased 1.5% (0%, 2.9%) and 1.5% (0.5%, 2.8%) 1-h and 21-h post exposure to silver, respectively. Urinary DNA oxidation marker 8­hydroxy­deoxy­guanosine increased 14% (6.4%, 21%) 1-h post exposure to copper; urinary neural marker vanillylmandelic acid increased 29% (3%, 54%) 1-h post exposure to aluminum; and urinary cortisol increased 88% (0.9%, 176%) 1-h post exposure to vanadium. Results for OP were expressed as change (%) from daily pre-exposure biomarker levels after exposure to ascorbate-related OP at a level equivalent to the mean concentration, or for exposure to glutathione-related OP at a level above the limit of detection. Exposure to ascorbate- or glutathione-related OP was significantly associated with increased inflammatory and neural biomarkers including interleukin-6, VEGF, UCHL1, and S100 calcium-binding protein B in blood, and malondialdehyde and 8-hydroxy-deoxy-guanosine in urine. For example, UCHL1 increased 9.4% (1.8%, 17%) in blood 21-h post exposure to ascorbate-related OP, while urinary malondialdehyde increased 19% (3.6%, 35%) and 8-hydroxy-deoxy-guanosine increased 24% (2.9%, 48%) 21-h post exposure to ascorbate- and glutathione-related OP, respectively. CONCLUSION: Our results from this exploratory study suggest that metal constituents and OP in ambient PM may influence biomarker levels associated with systemic inflammation, oxidative stress, perturbations of neural function, and systemic physiological stress.

Increased oxidative stress parameters in children with moderate iodine deficiency.

BACKGROUND: Iodine is a part of thyroid hormones and has been reported to act directly as an antioxidant or induce indirectly antioxidant enzymes. This study aimed to assess the urinary iodine concentration and its relationship between the antioxidant and oxidative stress capacity in healthy school-aged children. METHODS: In total, 196 students from five primary schools, randomly selected between 9 and 12 years (mean age: 10.2±1.2 years), were enrolled in the study. Urinary iodine levels were measured by spectrophotometry with the Sandell-Kolthoff reaction. Total antioxidant status (TAS) and total oxidant status (TOS) were analysed from urine samples. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of oxidative status. RESULTS: Fifty-four percentage (107) of the children had iodine deficiency (ID) and the majority of them (30%) had mild ID. There was no severe-ID child in the population (<20 µg/L). Urine TAS levels were significantly lower in the moderate-ID group than in the mild-ID group (6.5±4.1 vs. 11.3±4.1 mmol, p<0.001) and the iodine-sufficient group (11.0±5.3 µmol, p<0.001). TOS levels and OSI were found higher in the moderate-ID group than in the mild-ID group (4.8±2.1 vs. 3.7±2.1 µmol, p<0.001) and the iodine-sufficient group (4.8±2.1 vs. 3.4±2.5 mmol, p<0.001). In the moderate-ID group, low urine iodine levels exhibited significant negative correlations with OSI (r=-0.660) and TOS (r=-0.248) and a positive correlation with TAS (r=0.475). CONCLUSIONS: We found that children with moderate ID were exposed to more oxidative burden than children with mild ID or iodine sufficiency. Increased systemic oxidative stress induced by moderate ID could cause development of ID-related complications and diseases. Iodine supplementation could have a beneficial role in the prevention of oxidative stress.

Evidence of higher oxidative status in depression and anxiety.

We use a simple method for evaluating antioxidative status, by measuring the redox potential of urine, and correlate the findings with measures of anxiety and depression. We include 63 individuals (28 males and 35 females aged between 20 and 65 years). The validated anxiety State-Trait Anxiety Inventory questionnaire and the validated BDI (Beck Depression Inventory) questionnaire were used to evaluate anxiety and depression. Antioxidative status was determined by measuring the redox potential of urine collected in standard conditions. Correlation of the antioxidant capacity of urines evaluated using the ferric ion/specific dye method or through redox potential using the platinum electrode demonstrated the suitability of this last procedure. We found that normal anxiety state values corresponded to low urine redox potentials, whereas higher anxiety states were associated with high urinary redox potential. We also found that individuals with normal BDI values had significantly lower urine redox potentials than individuals with higher BDI values.

Increased inflammatory response and imbalance in blood and urinary oxidant-antioxidant status in South Indian women with gestational hypertension and preeclampsia.

OBJECTIVE: The objective of this study is to assess the association of blood and urinary oxidative stress parameters and inflammatory markers in women with gestational hypertension and preeclampsia. DESIGN AND METHODS: Malondialdehyde, protein bound sialic acid and C-reactive protein were estimated in serum and urine of pregnant women diagnosed with preeclampsia (n=30) and gestational hypertension (n=30) and the results were compared with 30 normal pregnant women. RESULTS: Whole blood glutathione level was reduced, and malondialdehyde and C-reactive protein levels were significantly higher and correlated with each other in preeclampsia (p<0.05). Urinary malondialdehyde significantly correlated with urinary protein bound sialic acid in preeclampsia (r=0.412; p=0.02). Receiver operating curve analysis of serum protein bound sialic acid and serum malondialdehyde showed reasonable cutoff values for the differential diagnosis of preeclampsia. CONCLUSIONS: Oxidative stress and inflammatory response are greater in women with preeclampsia in comparison to pregnant women with gestational hypertension and there is an association between oxidative stress and inflammatory response.

Six spectroscopic methods for detection of oxidants in urine: implication in differentiation of normal and adulterated urine.

Six separate methods to detect oxidants in urine were developed. The presence of the oxidants was established by initial oxidation of ferrous to ferric ion and detecting the ferric by chromogenic oxidation or complex formation. The reagents for chromogenic oxidation were N,N-dimethylamoino-1,4-phenylenediamine (DMPDA), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and 2-amino-p-cresol (APC), and the reagents for the chromogenic complex were xylenol orange (XO), 8-hydroxy-7-iodo-5-quinolinesulfonic acid (HIQSA), and 4,5-dihydroxy-1,3-benzene-di-sulfonic acid (HBSA). All methods showed comparable results when tested for ferric, chromate, permanganate, oxychloride, hydrogen peroxide, oxone, tert-butylhydroperoxide, and cumenehydroperoxide at a concentration of 1.0 mmol/L in water (CV < 7%). The nitrite results are comparable only with DMPDA and APC. Periodate responded to the highest oxidation number (ON = 8) by chromogenic oxidation but lowest (ON = 2) by the chromogenic complex. The iodate responded only to the chromogenic oxidation with ON = 6. The linearity of the procedures was established by chromate in water. The linear concentrations were 0.09-12.00 mE/L for DMPDA, ABTS, APC, and HBSA and 0.09-6.00 mE/L for XO and HIQSA. In all methods, the correlation coefficients were > or = 0.9991 and precisions were within +/- 5.6%. The methods were used to test oxidants in 238 urine specimens. The chromate at 3.0 mE/L in water was used as standard. The correlation coefficients of 0.9600-0.9853 and the ANOVA test (F = 0.90, F(critical) = 2.22 at P(0.48)) indicated that the methods correlated well. The median concentration of oxidants in the specimens was 0.21 mE/L with an average and standard deviation of 0.62 +/- 1.19 (range 0.04-8.83 mE/L). When Grubbs' statistical test was applied to the specimen results, no specimen was found to be outlier or could be considered as adulterated. The Grubbs' test also revealed that the threshold concentration to identify urine adulteration was 29 mE/L at confidence level of 99%.

Oxidant stress is a significant feature of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterised by an immunological, and often granulomatous, attack on bile ducts leading to fibrosis, cirrhosis, liver failure and death. Animal and human studies suggest that oxidant stress plays a key role in progression of other liver diseases, but no comprehensive investigation has been performed previously in PBC. A wide range of lipid peroxidation and antioxidant markers were measured in the blood and urine of 41 patients with histologically confirmed PBC. Lipid peroxidation markers were significantly elevated [plasma and urinary 8-isoprostane, P<0.001; plasma malondialdehyde (MDA), P=0.007] compared to age- and sex-matched controls. The most striking antioxidant depletion occurred with plasma total glutathione where levels were significantly reduced (30% of controls). Total serum antioxidant levels were decreased (P=0.013) and serum selenium and vitamin A were also lower (both P<0.001); vitamins C and E were normal. Most patients had early disease biochemically and were Child-Pugh grade A. Urinary 8-isoprostane correlated positively with Ludwig stage and markers of hepatic injury and cholestasis. This study clearly demonstrates that oxidant stress, as reflected in a comprehensive spectrum of lipid peroxidation and antioxidant markers, is a significant feature of early-stage PBC.

Multivitamin solutions for enteral supplementation: a source of peroxides.

OBJECTIVE: We investigated whether solutions of enteral vitamin supplementation are involved in the generation of peroxides and whether that contamination is biologically significant. METHODS: Peroxide contents of oral multivitamin preparations were measured over 3 wk after the initial opening of the containers. In selected premature infants (younger than 35 wk gestation), urinary peroxides were measured after initiating oral multivitamin supplementation. RESULTS: Peroxides in multivitamin solutions for enteral use are predominantly organic peroxides because they resist catalase. After the initial opening of the containers, there was a two-fold increase in total peroxides levels (P < 0.05) even in the preparation without riboflavin, a catalyst for the generation of peroxides. Initiation of oral vitamin supplementation was associated with increased (P < 0.05) urine peroxide levels. The high organic peroxide load did not correlate with its urinary excretion, mostly in the form of H(2)O(2). The excretion of H(2)O(2) corresponded to its oral intake from the multivitamin solution. CONCLUSIONS: Compared with parenteral multivitamin solutions, the enteral preparations contained higher organic peroxide levels starting with the initial opening of the bottles. The increased urinary excretion of H(2)O(2) after enteral multivitamin supplementation suggested a systemic diffusion of peroxides or of components of the multivitamin preparation responsible for the generation of peroxides. This oxidant load was not quenched by the immature antioxidant defenses of premature infants.

Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats.

1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. 2. Quercetin induced a significant reduction in systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood pressure. 4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%, P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as compared to WKY rats. However, in quercetin-treated SHR rats both parameters were similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the antioxidant properties of the drug.

Nutraceutical interventions may delay aging and the age-related diseases.

Largely due to better control of infectious diseases and to year-round access to a more nutritious diet, life expectancy in developed countries has increased dramatically in the twentieth century. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as Alzheimer's, Parkinson's, cardiovascular disease, cancer, arthritis, osteoporosis, benign prostatic hyperplasia, late-onset diabetes, and macular degeneration have increased. To obtain further significant improvements in both lifespan and the quality of life in this century, treatments and nutritional changes that address the age-related diseases and the aging process itself need to be examined and validated. There are many reports suggesting that oxidative stress and certain nutritional deficiencies may contribute to the aging process and to many age-related diseases. In this article, we report on two human clinical trials using novel antioxidant supplements in which urinary oxidative stress is significantly reduced. We also discuss the conceptual basis and existing literature for several nutritional supplements that may have beneficial effects on aging and age-related diseases. Based on the available data, we suggest that human life expectancy can be significantly increased in the twenty-first century by optimizing diet and using nutritional supplements.

Dietary precursors of trimethylamine in man: a pilot study.

An increased urinary excretion of trimethylamine and its N-oxide were observed in man following the oral intake (15 mmol) of choline (63% dose as trimethylamine and its N-oxide), D,L-carnitine (31% dose) and trimethylamine N-oxide (78% dose). Similar ingestion of betaine, creatinine or lecithin failed to elicit any significant increases. Of 46 different foods investigated, only fish and other sea-products gave rise to significant increases in urinary trimethylamine and N-oxide. Ingestion of fruits, vegetables, cereal and dairy produce, and meats had no measurable effects. Reasons for the apparent lack of trimethylamine provision by foods previously thought to be precursors are given and the role of gut microflora highlighted.

[Diagnosis of "fish odor syndrome" by urine nuclear magnetic resonance proton spectrometry]. / Diagnostic du "fish odour syndrome" par spectrométrie RMN proton des urines.

BACKGROUND: Trimethylaminuia is an unusual observation, often termed fish odor syndrome. The condition results from reduced ability to oxidize trimethylamine (TMA), which has a fishy odor, into odorless trimethylamine N-oxide (TMAO). METHOD: Proton nuclear magnetic resonance spectroscopy (MRS) was used as a simple and rapid method to detect TMA and TMAO in the same urine sample without pretreatment. Subjects were considered to have deficient N-oxidation of TMA if the TMAO/TMA ratio was greater than 80 p. 100 (heterozygous) or 65 p. 100 (homozygous). DISCUSSION: Direct proton RRS analysis of urine is well suited for diagnosis of fish odor syndrome. It can be used to detect heterozygous patients and also provides an easily implemented follow-up tool.