Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity

Background: Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, in early childhood. Chronic skin inflammation is associated with overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production of free radicals and antioxidant defense, results in tissue inflammation due to the upregulation of genes that encode inflammatory cytokines. This condition plays an important role in the pathogenesis of AD. Objective: To compare the antioxidant defense in children and adolescents with AD with that of healthy individuals and to verify the association of antioxidant defense with disease severity and nutritional status. Methods: Cross-sectional study that evaluated 48 children and adolescents with AD and 25 controls for nutritional assessment (body mass index z score [BMIZ] and height for age z score [HAZ]) and levels of vitamins A, C, E, and D, zinc (Zn), copper (Cu), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), high-sensitivity C-reactive protein (CRP) and interleukin 33 (IL-33). Results: There was no significant difference in the comparison between AD and control groups for serum levels of vitamins (A, D, C, and E), copper, and antioxidant enzymes. Serum zinc levels were higher in the AD group (β = 24.20; 95% CI 13.95–34.91; P < 0.001) even after adjusting the BMIZ, HAZ, gender, IL-33, and CRP. Children and adolescents with moderate or severe AD compared to mild AD (SCORAD – 36.7±17.4 vs 11.8 ± 3.9; P < 0.001) had lower values of the vitamin E/total lipid ratio (3.68 [0.29;12.63] vs 5.92 [3.27;17.37]; P = 0.013) (AU)

The effects of Oradexone and Ambroxol pretreatment of the oxidative sensitivity of the red blood cells in preterm infants.

The antioxidant enzyme activities and lipid peroxidation in the red blood cells of cord blood were investigated and compared at different gestation times in preterm and full-term neonates, with and without pretreatment of the pregnant mothers with Oradexone (Dexamethasone) or Ambroxol. Administration of the two drugs not only stimulated the lung surfactant system, but also exerted favourable effects on the antioxidant enzyme activities while the lipid peroxidation was decreased.

Phycoerythrin fluorescence-based assay for peroxy radicals: a screen for biologically relevant protective agents.

Under the conditions of this assay, antioxidants that react rapidly with peroxy free radicals (e.g., ascorbate, vitamin E analogs, urate), protect phycoerythrin completely from damage by such radicals generated by thermal decomposition of 2,2'-azobis(2-amidinopropane); other compounds provide partial concentration-dependent protection. Change in phycoerythrin fluorescence emission with time provides a measure of the rate of free radical damage. The assay exploits the unusual reactivity of phycoerythrin toward these peroxy radicals. On a molar basis, phycoerythrin reacts with these radicals over 100-fold slower than do ascorbate or vitamin E analogs, but over 60-fold faster than other proteins. Applications of this assay to the estimation of the peroxy radical scavenging capacity of human plasma are described, and to the comparison of the scavenging properties of several proteins and of DNA, of vitamins and their derivatives, of catecholamine neurotransmitters, and of a variety of other low molecular weight biological compounds.

[Changes in anti-oxidative homeostasis in hemodialysis patients]. / Veränderungen der antioxidativen Homöostase bei Hämodialysepatienten.

Changes of the antioxidative homoeostasis in hemodialysis patients were registered by determination of the antioxidative capacity (AC). This capacity has been increased before dialysis and decreased by 50% during dialysis. After 30 minutes of dialysis the AC was much more decreased than creatinine and urea. The cause of this AC reduction is not only a loss of antioxidants into the dialysate, but possibly also an oxygen radical formation by C5a-activated granulocytes, sequestered in pulmonary capillaries during transient leucopenia.

[Correlation of the antioxidant and coagulating blood systems under physiologic conditions]. / Korreliatsiia antioksidantoi i svertyvaiushchei sistemy krovi v fiziologicheskikh usloviiakh.

Examinations carried out on intact animals and healthy people have revealed a paired and multiple correlation with exists between thromboplastic properties of erythrocytes, the level of malondialdehyde accumulation in their membranes and the superoxide dismutase activity.

[State of lipid peroxidation system and antioxidant defense in acute respiratory viral infection in children and the principles of pathogenetic therapy]. / Sostaianie sistemy perekisnoe okislenie lipidov--antioksidantnaia zashchita pri ostroi respiratornoi virusnoi infektsii u detei i printsipy patogeneticheskoi terapii.

Summary. Altogether 187 young children presenting with acute respiratory viral infection were examined for lipid peroxidation and antioxidant defense. The principles of the pathogenetically validated antioxidant treatment are discussed.

[Relations between antioxidant activity and lipid state of blood as an indicator of the effect of tumor on the body]. / Vzaimosviaz' antiokislitel'noi aktivnosti i sostava lipidov krovi kak pokazatel' vliianiia opukholi na organizm.

Studies on antioxidant activity and lipid profile of erythrocytes and blood plasma in patients with fibroadenoma, fibrous-cystic mastopathy and neoplasia at different stages of progression showed each pathology to be associated with certain changes in the said parameters. Identification of signs of systemic effect of cancer growth was attempted. Malignant tumor was shown to involve at certain stage pronounced quantitative changes in lipid metabolism and erythrocyte membrane properties. These included changes in cholesterol/phospholipids molar ratio, presence of phosphatidylinositides and dissociation of regulatory links between antioxidant activity and cellular lipid profile in erythrocytes.

Biochemical indicators related to antioxidant status and bone metabolic activity in Finnish elderly men.

Serum concentrations of vitamins A, D and E, osteocalcin, calcium, selenium, cholesterol and HDL-cholesterol were measured in 270 elderly Finnish men aged from 65 to 84 years. alpha-Tocopherol and selenium decreased with aging as did 25-hydroxyvitamin D. Low serum levels were found especially for 25-hydroxyvitamin D (19% less than 8 micrograms/l), selenium (45% less than 70 micrograms/l) and osteocalcin (52% less than 1.8 micrograms/l). Men living in institutions for the aged had lower serum 25-hydroxyvitamin D levels than those living at home. Smoking was associated with decreased and alcohol consumption with increased serum levels of 25-hydroxyvitamin D. Those men who reported having most weekly working hours had highest serum levels of 25-hydroxyvitamin D. Serum osteocalcin correlated with 25-hydroxyvitamin D at normal or high serum vitamin levels but not at low vitamin levels; neither did it correlate with age or consumption of tobacco, alcohol or multivitamin pills.

Antioxidant defenses and lipid peroxidation in human blood plasma.

The temporal disappearance in human blood plasma of endogenous antioxidants in relation to the appearance of various classes of lipid hydroperoxides measured by HPLC postcolumn chemiluminescence detection has been investigated under two types of oxidizing conditions. Exposure of plasma to aqueous peroxyl radicals generated at a constant rate leads immediately to oxidation of endogenous ascorbate and sulfhydryl groups, followed by sequential depletion of bilirubin, urate, and alpha-tocopherol. Stimulating polymorphonuclear leukocytes in plasma initiates very rapid oxidation of ascorbate, followed by partial depletion of urate. Once ascorbate is consumed completely, micromolar concentrations of hydroperoxides of plasma phospholipids, triglycerides, and cholesterol esters appear simultaneously, even though sulfhydryl groups, bilirubin, urate, and alpha-tocopherol are still present at high concentrations. Nonesterified fatty acids, the only lipid class in plasma not transported in lipoproteins but bound to albumin, are preserved from peroxidative damage even after complete oxidation of ascorbate, most likely due to site-specific antioxidant protection by albumin-bound bilirubin and possibly by albumin itself. Thus, in plasma ascorbate and, in a site-specific manner, bilirubin appear to be much more effective in protecting lipids from peroxidative damage by aqueous oxidants than all the other endogenous antioxidants. Hydroperoxides of linoleic acid, phosphatidylcholine, and cholesterol added to plasma in the absence of added reducing substrates are degraded, in contrast to hydroperoxides of trilinolein and cholesterol linoleate. These findings indicate the presence of a selective peroxidase activity operative under physiological conditions. Our data suggest that in states of leukocyte activation and other types of acute or chronic oxidative stress such a simple regimen as controlled ascorbate supplementation could prove helpful in preventing formation of lipid hydroperoxides, some of which cannot be detoxified by endogenous plasma activities and thus might cause damage to critical targets.

High-performance liquid chromatographic determination of a 21-aminosteroid antioxidant in plasma.

A novel 21-aminosteroid, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1- piperazinyl]-16 alpha-methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate (I), is under development for the treatment of central nervous system injury in humans. This report describes a reversed-phase high-performance liquid chromatographic (RP-HPLC) method using ultraviolet detection at 254 nm for the determination of I in plasma with low nanogram per milliliter sensitivity. Plasma was deproteinated by mixing with acetonitrile and centrifuging, and I was extracted from the supernatant with disposable bonded-phase columns. The extracts were chromatographed on an octylsilane bonded-phase HPLC column with an acetonitrile-water mobile phase containing triethylammonium acetate, pH5. Quantification was accomplished by peak-height ratio analysis using an analogue of I as the assay internal standard. The method was suitable for the determination of I following a 30 mg/kg intraperitoneal dose in the rat.

Metabolic and nutritional parameters in patients after colonic polypectomy.

Breath methane and hydrogen, plasma acetate, serum selenium, vitamin A and beta-carotene were measured in 47 patients from whom colonic polyps had been removed by endoscopic polypectomy between 3 months and 2 years previously. Patients were compared with 39 control subjects in whom no abnormality was detected during colonoscopy. The proportion of methane exhalers was significantly (p less than 0.0005) higher in patients after polypectomy (66.0%) than in controls (28.2%). Mean plasma acetate was lower (p less than 0.025) in post-polypectomy patients (70.5 microM) than in control subjects (97.1 microM) while breath hydrogen was similar in both groups. The serum concentrations of the antioxidants selenium and beta-carotene showed no differences between the groups whereas vitamin A was higher (p less than 0.01) in serum samples of patients after polypectomy than of controls. These findings indicate that the colonic environment in post-polypectomy patients exhibits certain characteristics which may be related to the formation of benign tumors and possibly colon cancer.

Antioxidant activity of albumin-bound bilirubin.

Bilirubin, when bound to human albumin and at concentrations present in normal human plasma, protects albumin-bound linoleic acid from peroxyl radical-induced oxidation in vitro. Initially, albumin-bound bilirubin (Alb-BR) is oxidized at the same rate as peroxyl radicals are formed and biliverdin is produced stoichiometrically as the oxidation product. On an equimolar basis, Alb-BR successfully competes with uric acid for peroxyl radicals but is less efficient in scavenging these radicals than vitamin C. These results show that 1 mol of Alb-BR can scavenge 2 mol of peroxyl radicals and that small amounts of plasma bilirubin are sufficient to prevent oxidation of albumin-bound fatty acids as well as of the protein itself. The data indicate a role for Alb-BR as a physiological antioxidant in plasma and the extravascular space.

The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma.

The Total (Peroxyl) Radical-trapping Antioxidant Parameter (TRAP) of six freshly prepared human plasma samples and 45 frozen plasma samples has been determined. It is shown that contributions from urate (35-65%), plasma proteins (10-50%), ascorbate (0-24%) and vitamin E (5-10%) to TRAP account for all of the peroxyl radical-trapping antioxidant activity in the majority of the samples. The changes in concentrations of the plasma antioxidants during peroxyl radical attack show that the first line of defense is provided by the plasma sulfhydryl groups, even urate being spared during the initial stages of the reaction. The modes of action of all of these plasma antioxidants and possible interactions between them are discussed, with particular emphasis on the abilities of the water-soluble antioxidants to regenerate or spare the only lipid-soluble antioxidant, vitamin E.

Thin-layer chromatographic analysis of phenolic age resisters in elastomers in contact with the body, drugs and foods.

Phenolic antioxidants were identified by thin-layer chromatography in 102 samples of medical and pharmaceutical rubber articles. Acetone extracts of rubber were spotted on silica gel plates with a concentrating zone. Benzene, benzene-hexane (75:25) and benzene-ethyl acetate-acetone (100:5:1) were used as developing solvents and N-chloro-2,6-dichloro-p-benzoquinone monoimine as spray reagent. Only 8 sterically hindered phenols among the 57 previously listed were found in current use. Reasons for choosing these compounds and the experimental conditions are discussed.