The kynurenine and serotonin pathway, neopterin and biopterin in depressed children and adolescents: an impact of omega-3 fatty acids, and association with markers related to depressive disorder. A randomized, blinded, prospective study.

Depressive disorder is a severe mental condition. In addition to genetic factors, immunological-inflammatory factors, oxidative stress, and disturbances in neurotransmitter metabolism, kynurenine and serotonin pathways may play a role. The exact mechanisms, especially in depressed children and adolescents, are not fully understood. Our primary hypothesis was whether the metabolites of tryptophan degradation in children and adolescents with depressive disorder might be influenced by omega-3 FAs compared to omega-6 FAs during a 12-week supplementation. A secondary hypothesis was to investigate whether tryptophan metabolites in children and adolescents are associated with markers of inflammatory response, oxidative stress, cortisol, and the serum omega-6/omega-3 FA ratio. Metabolites of tryptophan degradation and pteridines, neopterin, and biopterin in urine were analyzed with an HPLC system. Surprisingly, omega-3 FAs stimulated both kynurenine (kynurenine/tryptophan ratio) and serotonin (5-hydroxytryptophan) pathways, whereas omega-6 FAs only increased the kynurenine/tryptophan ratio. Neopterin and biopterin were not different from the healthy controls. Biopterin increased after omega-3 FA supplementation. Serotonin was positively correlated with lipoperoxidation and a marker of oxidative protein damage. Of the monitored tryptophan metabolites, only 5-hydroxyindolacetic acid was positively correlated with the severity of depression, total cholesterol, and negatively with brain-derived neurotrophic factor and glutathione peroxidase. In conclusion, in children and adolescents, both supplemented FAs stimulated the kynurenine pathway (kynurenine/tryptophan ratio) and kynurenine formation. However, the serotonin pathway (5-hydroxytryptophan) was stimulated only by omega-3 FA. Tryptophan metabolism is associated with oxidative stress, inflammation, total cholesterol, and cortisol. We are the first to point out the association between the kynurenine pathway (KYN/TRP ratio) and the omega-6/omega-3 FA ratio. The metabolite 5-HIAA could play a role in the pathophysiology of depressive disorder in children and adolescents. Clinical Trial Registration: https://www.isrctn.com/ISRCTN81655012, identifier ISRCTN81655012.

Stress Hormones Cortisol and Aldosterone, and Selected Markers of Oxidative Stress in Response to Long-Term Supplementation with Omega-3 Fatty Acids in Adolescent Children with Depression.

Late childhood and adolescence are crucial periods of brain development with high vulnerability to environmental insults. The aim of this study was to test the hypotheses that in adolescents with depression (a) 12 weeks-supplementation with omega-3 fatty acids results in the attenuation of salivary stress hormone concentrations; (b) the mentioned supplementation improves potentially disrupted daily rhythm of stress hormones; (c) stress hormone concentrations correlate with values of selected markers of oxidative stress. The sample consisted of 60 patients suffering from depression aged 11-18 years. Hormone concentrations in saliva were measured in the morning and midday before (baseline) and after (6, 12 weeks) food supplementation with omega-3 or omega-6 (as comparator) fatty acids. Morning cortisol decreased in response to omega-3 but not omega-6 fatty acids at 12 weeks compared to baseline. No changes were observed in aldosterone concentrations. The obtained results show that adolescent children with depression preserved the daily rhythm of both stress hormones. Baseline morning cortisol concentrations correlated positively with depression severity and lipoperoxides, and negatively with docosahexaenoic acid. Aldosterone concentrations correlated positively with 8-isoprostane. Thus, both hormones showed positive correlation with the selected markers of oxidative stress suggesting that enhanced stress hormone secretion may be associated with increased oxidative tissue damage in adolescent children with depression. This study was registered with the ISRCTN registry (DEPOXIN study, ISRCTN81655012).

Oxidative Stress Markers and Antioxidant Enzymes in Children and Adolescents with Depressive Disorder and Impact of Omega-3 Fatty Acids in Randomised Clinical Trial.

Oxidative stress (OS) is thought to play a role in mental disorders. However, it is not clear whether the OS is the cause or consequence of the disorder. We investigated markers of oxidative stress (8-isoprostane (8-IsoP-U), lipoperoxides (LP), advanced oxidation protein products (AOPP) and nitrotyrosine (NT)) and antioxidant protection (Trolox equivalent antioxidant capacity (TEAC), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in 60 paediatric and adolescent patients with depressive disorder (DD) compared to healthy controls. The patients were divided into two groups (1:1). One group received an emulsion of omega-3 fatty acid (FA), and the other group an emulsion of sunflower oil with omega-6 FA for 12 weeks. The levels of 8-IsoP-U, AOPP and NT were increased, and GPx activity was decreased in patients compared to the controls. We found a significant positive correlation of the Children's Depression Inventory score with NT and a negative correlation with TEAC, SOD and GPx. NT correlated positively with the baseline omega-6/omega-3 FA ratio and a negatively with SOD. A supplementation with omega-3 FA, but not with omega-6 FA, decreased 8-IsoP-U, AOPP, NT levels and increased TEAC and SOD activity. Our results suggest that NT may play a role in the pathophysiology of DD, while elevated isoprostane is likely caused by the high omega-6/omega-3 FA ratio. Omega-3 FA supplementation reduces oxidative stress in patients with DD. This study was registered with the ISRCTN registry (ISRCTN81655012).

The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders.

The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.

The Effect of Omega-3 Fatty Acids on Thromboxane, Brain-Derived Neurotrophic Factor, Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial.

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child's Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).

Lipid Profile, Lipoprotein Subfractions, and Fluidity of Membranes in Children and Adolescents with Depressive Disorder: Effect of Omega-3 Fatty Acids in a Double-Blind Randomized Controlled Study.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids such as total cholesterol (TCH), LDL-, and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. The primary endpoint of the study was the effect of omega-3 FA on the severity of depression in children and adolescents. This study aimed to investigate the secondary endpoint, relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities, and erythrocyte membrane fluidity in 58 depressed children and adolescents (calculated by the statistical program on the effect size), as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, and LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. Improvement of symptoms in the group supplemented with a fish oil emulsion rich in omega-3 FA in contrast to omega-6 FA (emulsion of sunflower oil) has been observed. We are the first to report that omega-3 FAs, but not omega-6 FA, increase large HDL subfractions (anti-atherogenic) after 12 weeks of supplementation and decrease small HDL subfractions (proatherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and the large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder. The study was registered under ISRCTN81655012.

Lower activity of salivary alpha-amylase in youths with depression.

Measurement of basal and stress-induced salivary alpha-amylase activity may help to understand autonomic nervous system disturbance in mental disorders. The potential sympathetic nervous system dysregulation in children and adolescent psychopathologies is mostly unknown. The present study was aimed to test the hypothesis that salivary alpha-amylase activity is higher in youths diagnosed with depression than in healthy subjects considering a part of the daily rhythm of enzyme activity and its morning to midday slope. A total of 30 children aged 15 ± 0.46 years (15 patients with depression, 4 boys, 11 girls, and 15 sex- and age-matched healthy controls) participated in the study. Two saliva samples were collected from each subject to measure activity of alpha-amylase in the morning and midday. The results of the present study revealed that the midday but not morning alpha-amylase activity was lower in patients with depression than in healthy controls. The diurnal increase in enzyme activity present in healthy subjects was absent in patients. The children and adolescents with depression exhibited flatter morning to midday slopes of alpha-amylase activity. In conclusion, the present results indicate a disturbance of alpha-amylase daily rhythm in youths with depression and motivate further studies on the relationship between sympathetic activation and mood disorders.

The Oak-wood Extract Robuvit® Improves Recovery and Oxidative Stress after Hysterectomy: A Randomized, Double-blind, Placebo-controlled Pilot Study.

Hysterectomy has a variety of medical indications and improves pre-operative symptoms but might compromise the quality of life during recovery due to symptoms such as fatigue, headache, nausea, depression, or pain. The aim of the present study was to determine the effect of a standardized extract from French oak wood (Quercus robur) containing at least 40% polyphenols of the ellagitannins class, Robuvit®, on convalescence and oxidative stress of women after hysterectomy. Recovery status was monitored with the SF-36 questionnaire. The supplementation with Robuvit® (300 mg/day) during 4 weeks significantly improved general and mental health, while under placebo some items significantly deteriorated. Oxidative stress and enhancement of MMP-9 activity was significantly reduced by Robuvit® versus placebo. After 8 weeks of intervention, the patients' condition improved independently of the intervention. Our results suggest that the use of Robuvit® as a natural supplement relieves post-operative symptoms of patients after hysterectomy and reduces oxidative stress. The study was registered with ID ISRCTN 11457040 (13/09/2019).

Constituents and Metabolites of a French Oak Wood Extract (Robuvit®) in Serum and Blood Cell Samples of Women Undergoing Hysterectomy.

Ellagitannins are signature constituents of oak wood and their consumption has been associated with various health benefits. In vivo, they undergo metabolic degradation including gut microbial metabolism yielding urolithins. Only limited data is available about compounds being present in blood after intake of an extract from French oak wood, Robuvit®. In the course of a randomized, double-blind, controlled clinical investigation, 66 patients undergoing hysterectomy received placebo or 300 mg Robuvit® per day before and over 8 weeks after surgery. Serum and blood cell samples were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The number of urolithin producers and the urolithin levels increased after intake of Robuvit®. In serum samples, the median concentration of urolithin A was 14.0 ng/ml [interquartile range (IQR) 57.4] after 8 weeks. Urolithin B was determined at 22.3 ng/ml (IQR 12.6), urolithin C at 2.66 ng/ml (IQR 2.08). In blood cells, lower concentrations and only urolithins A and B were detected. A statistically significant association of lower post-surgical pain scores with metabotype A was detected (p < 0.05). To conclude, supplementation with French oak wood extract raised urolithin generation in patients and suggested health advantages for urolithin-producers.

Omega-3 fatty-acids modulate symptoms of depressive disorder, serum levels of omega-3 fatty acids and omega-6/omega-3 ratio in children. A randomized, double-blind and controlled trial.

Omega-3 fatty acids (FA) are a promising adjuvant therapy for depressive disorder (DD) in adults. The objective of this single-centre, randomized, double-blind and controlled study was to compare the efficacy of an omega-3 FA fish oil emulsion with a control oil emulsion alongside the standard treatment for depression in children and adolescents suffering from DD or mixed anxiety depressive disorder (MADD) and to analyse serum fatty acid levels and omega-6/omega-3 FA ratio before and after the intervention. 60 children were randomised 1:1 to the intervention (Om3) or active comparator (Om6) groups. Children's Depression Inventory (CDI) ratings were performed at the baseline, every 2 weeks for a 12-week intervention period. Significant reductions in CDI scores were observed after 6 and 12 weeks of intervention in the Om3 group and in the DD subgroup compared to the Om6 and MADD subgroup. Ratio of omega-6/omega-3 decreased in Om3 but not in Om6 from 24.2/1 to 7.6/1 after 6 weeks, EPA, omega-6/omega-3 ratio, but not DHA, correlated with severity symptoms at the baseline. An omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant supplement during the treatment of depressive disorders in children. Trial registration: ISRCTN 81655012.

Neuroinflammation and depressive disorder: The role of the hypothalamus.

Data accumulated over the last two decades has demonstrated that hypothalamic inflammation plays an important role in the etiopathogenesis of the most prevalent diseases, such as cardiovascular diseases, metabolic syndrome, and even cancer. Recent findings indicate that hypothalamic inflammation is also associated with stress exposure and certain psychiatric diseases, such as depressive disorder. Mechanistic studies have shown that intense and/or chronic stress exposure is accompanied by the synthesis of inflammatory molecules in the hypothalamus, altered hypothalamic-pituitary-adrenal axis activity, and development of glucocorticoid resistance. Consequently, these factors might play a role in the etiopathogenesis of psychiatric disorders. We propose that hypothalamic inflammation represents an interconnection between somatic diseases and depressive disorder. These assumptions are discussed in this mini-review in the light of available data from studies focusing on hypothalamic inflammation.

Gender differences in LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke and their association with oxidative stress markers.

The aim of our study was to examine gender differences of LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke with focus on small LDL and HDL subfractions, and their association with oxidative stress markers. In addition, we have monitored the 7-day effect of cholesterol-lowering drugs administered to patients after the acute ischemic stroke, on these subfractions. Eighty two stroke patients and 81 age matched controls were included in this study. Blood was collected from patients within 24 h after the stroke (group A) and re-examined at the 7-day follow-up (group B). We have found gender differences in LDL- and HDL-subfractions in stroke patients, lipid-lowering drugs administered to acute ischemic stroke patients significantly reduced all measured parameters of lipoprotein profile. In the group A LDL1 subfraction positively correlated with activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) indicating a protective role of this subfraction. On the contrary, small HDL subfractions positively correlated with lipoperoxide levels and negatively with trolox equivalent antioxidant capacity in plasma suggesting a negative role of these subfractions. In this work we have confirmed the hypothesis of atherogenic properties of small HDL subfractions and anti-atherogenic properties of large LDL1-subfractions.

Fish oil emulsion supplementation might improve quality of life of diabetic patients due to its antioxidant and anti-inflammatory properties.

Diabetes-related complications, including cardiovascular disease, retinopathy, nephropathy, and neuropathy, are a significant cause of increased morbidity and mortality among people with diabetes. Previous studies have confirmed that hyperglycemia has pro-oxidative and proinflammatory properties which cause diabetic complications. We hypothesized that supplementation of fish oil emulsion (FOE), rich in omega-3 polyunsaturated fatty acids, to diabetic patients might reduce hyperglycemia-induced pathological changes due to specific properties of FOE. Omega-3 polyunsaturated fatty acids have a wide range of biological effects. In this project, we have examined the potential protective effect of the FOE on hyperglycemia-induced oxidative stress and cytokine generation in monocytes/macrophages U937 system in vitro. The monocytes/macrophages U937 were cultivated under normal or hyperglycemic (35 mmol/L glucose) conditions with/without FOE for 72 hours. We have focused on specific markers of oxidative stress (antioxidant capacity; superoxide dismutase activity; oxidative damage to DNA, proteins, and lipids) and inflammation (tumor necrosis factor, interleukin-6, interleukin-8, monocytic chemotactic protein-1). Hyperglycemia caused reduction of antioxidant capacity, induction of DNA damage, and proinflammatory cytokine secretion. FOE significantly increased antioxidant capacity of cells as well as superoxide dismutase activity and significantly reduced tumor necrosis factor, interleukin-6, interleukin-8, and monocytic chemotactic protein-1 release. No effect was observed on oxidative damage to DNA, proteins, and lipids. Our results indicate that FOE can reduce hyperglycemia-induced pathological mechanisms by its antioxidant and anti-inflammatory properties.

Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents: a pilot study.

BACKGROUND: The prevalence of mood disorders in children is a growing global concern. Omega-3 fatty acids (FA) are emerging as a promising adjuvant therapy for depressive disorder (DD) in paediatric patients. The primary objective of this pilot, single-centre, randomized, double-blind controlled study was to compare the efficacy of an Omega-3 FA fish oil emulsion with a control oil emulsion alongside standard treatment for depressive symptoms in children and adolescents suffering from depressive disorder (DD) and mixed anxiety depressive disorder (MADD). METHODS: 38 children (12 patients were treated and diagnosed for at least 1 month before enrolment, 26 patients were first-time diagnosed as DD) aged 11-17 years were randomised 1:1 to the intervention (Omega-3 FA, 19 patients) or active comparator (Omega-6 FA, 19 patients) groups. Children's depression inventory (CDI) ratings were performed at baseline, every 2 weeks for a 12-week intervention period and at 4-week post-intervention. 35 patients (17 in Omega-3 and 18 in Omega-6 groups) who completed the whole intervention period were evaluated. Patients from Omega-3 group were stratified according to diagnosis into two subgroups (DD-10/17 and mixed anxiety depressive disorder (MADD)-7/17 patients) and in the Omega-6 group into DD-10/18 and MADD-8/18 patients. Groups were evaluated separately. Differences between-groups were tested with the Student´s t test or non-parametric Mann-Whitney U test. Two-way ANOVA with repeated measures and Friedman test were used to analyse the Treatment effect for response in CDI score. p < 0.05 was considered significant in all statistical analyses. RESULTS: Significant reductions in CDI scores in 35 analysed patients who completed 12 weeks intervention were observed after 12 weeks of intervention only in the Omega-3 group (p = 0.034). After stratification to depressive disorder and mixed anxiety depressive disorder subgroups, the DD subgroup receiving the Omega-3 FA fish oil showed statistically greater improvement (score reduction after 8 week treatment of -9.1 CDI, p = 0.0001) when compared to the MADD subgroup (score reduction after 8 week treatment -4.24 CDI, p = 0.271). CONCLUSIONS: CDI scores were reduced in the Omega-3 group and the depression subgroup had greater improvement than the mixed depressive/anxiety group. An Omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant supplement during the treatment of depressive disorders in children. Trial registration ISRCTN81655012.

Gas chromatography determination of fatty acids in the human erythrocyte membranes - A review.

Blood fatty acid measurements can reflect exogenously consumed fatty acids allowing to resolve some metabolic disorders (e.g. diabetes, anorexia) or mental disorders (e.g. depression, anxiety, schizophrenia). For this purpose, fatty acids can be determined in the whole blood or various blood fractions such as the plasma, serum or erythrocytes. Measurement of fatty acids in the whole blood by dried blood spot technique is becoming increasingly popular and is often used mainly for the screening of newborns due to the use of the small sample volume. The most popular is determination of fatty acids in plasma or serum samples. While the profile of plasma fatty acids fluctuates based on daily dietary intake, the red blood cell membrane composition of fatty acids reflects the 2-3 month dietary intake. Such results can be more reflective in contrast to the plasma/serum and therefore the present review will summarize available information on gas chromatography determination of fatty acids in human red blood cell membranes. Selection of extraction and derivatization reagents as well as presentation of chromatographic conditions will be discussed here.

High density lipoprotein subfractions and paraoxonase 1 in children.

The Lipoprint system (Quantimetrix Corp., CA, USA), enables the determination of 10 high density lipoprotein (HDL) subfractions in contrast to the 5 HDL subfractions that can be determined by ultracentrifuge analysis. HDL subfractions, and their relationships to the arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1), together with total-, very low density lipoprotein- and low density lipoprotein (LDL)-cholesterol and LDL subfractions were investigated in the serum of 27 mildly hypercholesterolemic children and 21 healthy controls. Our results suggest the antiatherogenity of large HDL (L-HDL) subfractions and the atherogenity of small HDL (S-HDL) subfractions in the study groups. However, the relationship between the intermediate HDL (I-HDL) subfractions with the LDL subfractions and other lipoproteins did not suggest that I-HDL subfractions are antiatherogenic. No significant association between PON1-A and the HDL subfractions was found. In contrast, PON1-L activity positively correlated with the antiatherogenic large HDL1 subfraction and negatively with intermediate HDL subfractions 4, 5 and 6. Our results contribute to the knowledge of the roles of total HDL and ten individual HDL subfractions in children and adolescents.

Protective effects of black tea extract against oxidative DNA damage in human lymphocytes.

The aim of the present study was to examine the genoprotective and radioprotective effects of black tea extract (BTE) against the induction of single strand DNA breaks in human lymphocytes subjected to hydrogen peroxide (H2O2) or gamma-rays (2 Gy dose). Lymphocytes were incubated with or without different concentrations of BTE (0.005-500 µg/ml) for 30 min, followed by treatment with or without H2O2 (0.088 µmol/l) for 5 min. To examine the radioprotective effect of BTE, the lymphocytes were incubated with or without BTE for 30 and 60 min prior to and following in vitro irradiation. Oxidative damage to DNA was monitored using a comet assay. BTE at lower concentrations prevented H2O2-induced DNA damage. An increase in BTE concentrations resulted in increased formation of single strand DNA breaks. BTE also exerted significant protective effects against gamma radiation-induced total DNA damage in healthy lymphocytes during their 30 or 60 min incubation with BTE prior to or following irradiation. Therefore, the protective effect of BTE against irradiation was time-dependent. The results contribute to the research on potential beneficial effects of natural compounds, such as BTE, in cancer and its protective effects of normal tissue during radiation therapy.

Changed Plasma Levels of Zinc and Copper to Zinc Ratio and Their Possible Associations with Parent- and Teacher-Rated Symptoms in Children with Attention-Deficit Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) is associated with alterations in the metabolism of some trace elements which may participate in the pathogenesis of this disorder. The aims of the present study were to investigate the trace element status (copper (Cu), zinc (Zn), copper to zinc ratio (Cu/Zn ratio), selenium (Se), and lead (Pb)) of ADHD children and compare them with the control group. Associations between examined elements and ratings of ADHD symptoms were also assessed. Fifty-eight ADHD children and 50 healthy children (aged 6-14 years) were included in the study. The concentrations of Cu, Zn, and Se in the plasma and Pb in the whole blood were measured by atomic absorption spectrometry. We found lower Zn level (p = 0.0005) and higher Cu/Zn ratio (p = 0.015) in ADHD children when compared with the control group. Copper levels in ADHD children were higher than those in the control group, but not significantly (p > 0.05). No significant differences in levels of Se and Pb between both groups were found. Zinc levels correlated with parent-rated score for inattention (r = -0.231, p = 0.029) as well as with teacher-rated score for inattention (r = -0.328, p = 0.014). Cu/Zn ratio correlated with teacher-rated score for inattention (r = 0.298, p = 0.015). Significant associations of Se and Pb with parent- and teacher-rated symptoms were not observed. The results of this study indicate that there are alterations in plasma levels of Cu and Zn as well as significant relationships to symptoms of ADHD.

Sex differences in the blood antioxidant defense system in juvenile rats with various genetic predispositions to hypertension.

This study investigated the contribution of blood oxidative stress (OS) to the development of hypertension, as well as sex differences in the antioxidant defense system (ADS) in genetic models of hypertension. Nine-week-old normotensive Wistar-Kyoto (WKY) rats, borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR) of both sexes were used. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography, the trolox equivalent antioxidant capacity (TEAC) and the concentration of lipid peroxides (LP) were determined in plasma. The activity of the antioxidant enzymes Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was determined in erythrocytes. SBP was significantly elevated in BHR and SHR in both sexes. BHR and SHR males had a higher SBP than the respective females. Sex-dependent differences in the ADS were found only in SHR, in which TEAC, SOD and CAT were significantly higher in males than in females. No differences in TEAC, SOD, CAT and GPx were observed between BHR (males and females) and WKY controls. LP levels were similar in all the groups investigated. Significant positive correlations were observed between SBP and both SOD and CAT. TEAC correlated positively with SOD and LP. As no signs of oxidative damage to lipids were found in young BHR and SHR of either sex, OS in the blood does not seem to be causatively related to the development of hypertension in these rats. However, despite activated antioxidant defenses, the positive correlation between plasma TEAC and LP suggests that oxidative damage is progressing slowly and therefore it seems to be a consequence rather than the cause of hypertension.