In vitro and in silico study of the biological activity of tetradentate Schiff base copper(II) complexes with ethylenediamine-bridge.

The biological activity of six structurally similar tetradentate Schiff base copper(II) complexes, namely [Cu(ethylenediamine-bis-acetylacetonate)] (CuAA) and five derivatives where two methyl groups are replaced by phenyl, (CuPP), CF3 (CuTT) or by mixed groups CH3/CF3 (CuAT), Ph/CF3 (CuPT), and Ph/CH3 (CuAP) has been investigated. The set of antioxidant assays was performed, and the results were expressed as IC50 and EC50 values. The series of complexes showed interesting bioactivity and were investigated for the determination of antioxidant, antifungal, antimicrobial, and cytotoxic activity. A significant antioxidant behavior was exhibited by complex CuAA, greater than Trolox in the Oxygen Radical Absorbance Capacity (ORAC) assay. Antibacterial assay over Gram-positive and Gram-negative pathogenic bacterial strains and some fungal pathogens were studied. Antiproliferative activity of complexes in two human tumor cell lines, breast adenocarcinoma MCF-7, colon adenocarcinoma LS-174, and normal fibroblast cells-MRC-5, examined the effect on cell cycle progression. The significant cytotoxic potential, comparable to cisplatin cytotoxicity, was determined in human breast cancer cell line-MCF-7 with IC50 values being 17.53-31.40 µM and human colon cancer cell line-LS-174 with IC50 values being 15.22-23.92 µM. All tested compounds showed nearly twice more selectivity toward cancer cell lines than normal cells. The interactions of complexes with human serum albumin (HSA), the most prominent protein in plasma, were investigated using spectroscopic fluorescence techniques. The complexes bind to human serum albumin at multiple sites (n = 0.2-1.9), displaying a moderate binding constant Ka = 4.1-12.4 × 104 M-1. The molecular docking experiment effectively showed complex binding to HSA and DNA molecular fragments.

Half of expectant women in Montenegro show iodine deficiency, indicating that supplementation during pregnancy is necessary.

OBJECTIVE: In this study, iodine level in pregnant women of Montenegro and their needs for supplementation were investigated. METHODS: A urinary iodine concentration (UIC) study of 326 pregnant women between September and December 2017 in three regions of Montenegro was performed. UIC was related to creatinine (UI/Cr ratio). RESULTS: The median UIC (133 ± 5 µg/L) was indicative of iodine deficiency, as the WHO recommended UIC is 150-249 µg/L. The UI/Cr ratio (160 ± 6 µg/g creatinine) was just above the WHO/UNICEF/IGN recommendation. Approximately 50% of the surveyed women had a lower UIC than that recommended. CONCLUSION: Iodine deficiency is present in pregnant women in Montenegro. Monitoring the UIC during routine analyses in pregnant women in Montenegro is recommended, along with iodine supplementation for individuals that need it.

Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis.

Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.

Study on the assessment of humification processes during biodegradation of heavy residual fuel oil.

The aim of this study was to investigate the creation of humic substances during biodegradation of heavy residual fuel oil, because there are indications that substances similar to humic substances are generated during biodegradation of polycyclic aromatic hydrocarbons. In the study, which lasted for 110 days, biodegradation of heavy residual fuel oil was carried out in a layer of artificial soil substrate. The initial concentration of the total petroleum hydrocarbon in the prepared artificial soil substrate (biopile) was 23.1 g kg-1 dry weight (d.w.). At the end of the process, the total petroleum hydrocarbons were reduced to 8.1 g kg-1 d.w. in the inoculated biopile, while the content of humic acids increased during bioremediation from 3.15 g kg-1 d.w. to 4.95 g kg-1 d.w. The humic acids extracted from biopile during the biodegradation process were characterized by various chemical techniques (elemental analysis, spectrofluorimetric analysis, electrochemical measurements, and size exclusion chromatography). The results showed that levels of C, H and the H/C ratio decreased as the biodegradation process progressed. This indicated that humic acids aromatization process took place and this was confirmed by the spectrofluorimetric analysis. The increase of oxygen percentage and the O/C ratio in the humic acids after the biodegradation treatment indicated an increase in functional oxygen groups. Additional analyses of humic acids from the inoculated biopile showed that they were transformed during the bioremediation process. They had greater redox and buffering capacities and a larger portion of the fractions had high molecular mass. Also, the humification parameters (the CHAs/CFAs ratio and CHAs/Corg ratio) increased during the biodegradation. This is one of the few studies that describes the generation of humic substances during the biodegradation of oil compounds.

Effects of several atypical antipsychotics closapine, sertindole or ziprasidone on hepatic antioxidant enzymes: Possible role in drug-induced liver dysfunction.

Chronic use of atypical antipsychotics may produce hepatic damage. Atypical antipsychotics, including clozapine, sertindole, and ziprasidone, are extensively metabolized by the liver and this process generates toxic-free radical metabolic intermediates which may contribute to liver damage. The aim of this study was to investigate whether clozapine, sertindole, or ziprasidone affected hepatic antioxidant defense enzymes which consequently led to disturbed redox homeostasis. The expression and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferases (GST) were measured in rat livers at doses corresponding to human antipsychotic therapy. Clozapine increased activity of SOD types 1 and 2, GR and GST, but reduced CAT activity. Sertindole elevated activities of both SODs. In ziprasidone-treated rats only decreased CAT activity was found. All three antipsychotics produced mild-to-moderate hepatic histopathological changes categorized as regenerative alterations. No apparent signs of immune cell infiltration, microvesicular or macrovesicular fatty change, or hepatocytes in mitosis were observed. In conclusion, a 4-week long daily treatment with clozapine, sertindole, or ziprasidone altered hepatic antioxidant enzyme activities and induced histopathological changes in liver. The most severe alterations were noted in clozapine-treated rats. Data indicate that redox disturbances may contribute to liver dysfunction after long-term atypical antipsychotic drug treatment.

Edaravone May Prevent Ferroptosis in ALS.

Radicava™ (Edaravone) was approved the Food and Drug Administration (FDA) as a new treatment for amyotrophic lateral sclerosis (ALS). Edaravone is a synthetic antioxidant that specifically targets oxidative damage interacting with lipid radicals in the cell. In ALS disease the multiple cell types are involved in devastating loss of motor neurons. Mutations and biochemical changes in various cell types jointly contribute to motor neuron death, disease onset, and disease progression. The overall mechanism of neurodegeneration in ALS is still not completely understood. Dying motor neurons have been reported to exhibit features of apoptosis. However, non-apoptotic features of dying motor neurons have also been reported such as ferroptosis. The role of Edaravone in the prevention of ferroptosis in parallel with other therapeutic approaches to ALS therapy is discussed.

Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content.

Antipsychotic drugs interfere with the antioxidant defense system provoking complex and often toxicological effects. Here we examined differences in plasma albumin reduced free thiol (SH) group content and its reactivity as a consequence of clozapine (CLZ) and ziprasidone (ZIP) binding. Chronic administration of CLZ reduced, whereas treatment with ZIP increased albumin-SH content in rats. Regardless of the ratio of stearic acid (SA) bound to protein, in vitro binding of ZIP to human serum albumin (HSA) increased both the SH group level and reactivity. In contrast, the effect of CLZ on HSA-SH reactivity was dependent on HSA to SA molar ratio. CLZ binding was accompanied by an increase in HSA-SH reactivity in samples with normal, but a reduction of its reactivity level with higher SA/HSA ratio, compared to drug-free samples. We demonstrate by steady-state fluorescence quenching studies that an increase in SA binding to HSA is associated with a significant reduction of binding constant for both antipsychotics. In addition, this is the first report of quantitative characterization of ZIP binding to HSA. Our findings suggest that albumin-SH content and reactivity is modulated by ZIP towards an increased antioxidant defense capacity in circulation, as opposed to CLZ, which can contribute to the safer, more effective treatment of schizophrenia.

Biliverdin-copper complex at physiological pH.

Biliverdin (BV), a product of heme catabolism, is known to interact with transition metals, but the details of such interactions under physiological conditions are scarce. Herein, we examined coordinate/redox interactions of BV with Cu2+ in phosphate buffer at pH 7.4, using spectrophotometry, HESI-MS, Raman spectroscopy, 1H NMR, EPR, fluorimetry, and electrochemical methods. BV formed a stable coordination complex with copper in 1 : 1 stoichiometry. The structure of BV was more planar and energetically stable in the complex. The complex showed strong paramagnetic effects that were attributed to an unpaired delocalized e-. The delocalized electron may come from BV or Cu2+, so the complex is formally composed either of BV radical cation and Cu1+ or of BV radical anion and Cu3+. The complex underwent oxidation only in the presence of both O2 and an excess of Cu2+, or a strong oxidizing agent, and it was resistant to reducing agents. The biological effects of the stable BV metallocomplex containing a delocalized unpaired electron should be further examined, and may provide an answer to the long-standing question of high energy investment in the catabolism of BV, which represents a relatively harmless molecule per se.

A Case Report of Exacerbation of Leg Ulcers Associated with Acute High-dose Acetylsalicylic Acid in a Patient with Klinefelter Syndrome.

Klinefelter syndrome (KS) is the most frequent type of congenital sex-chromosomal disorder caused by at least one extra X chromosome and commonly treated with lifetime testosterone therapy. Ulcerative lesions on lower extremities may occur as a complication of KS. The pathogenesis of ulcers in KS patients has not been clarified on a molecular level. Here we present a case of leg ulcers exacerbation associated with the administration of a high dose of acetylsalicylic acid in a 63-year-old KS patient with karyotype 47,XXY undergoing testosterone replacement therapy for the last 20 years. The appearance of the ulcer on the patient's leg occurred during one week of high oral acetylsalicylic acid intake (1.2 g daily). The patient was advised to return to his standard daily dose of 0.1 g of acetylsalicylic acid and significant improvement of his leg ulcer was observed after two weeks. We hypothesize that testosterone-mediated nitric oxide balance in KS patient is perturbed under the condition of acute high-dose acetylsalicylic acid administration. We propose that small standard doses of approximately 0.1 g/day of acetylsalicylic acid have no apparent effect on nitric oxide status, whereas higher doses may cause dysregulation of nitric oxide production and/or utilization, creating conditions which may cause the appearance of leg ulcers in the KS patients.

Coordination and redox interactions of ß-lactam antibiotics with Cu2+ in physiological settings and the impact on antibacterial activity.

An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight ß-lactam antibiotics using UV-Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These ß-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis.

Redox properties of transitional milk from mothers of preterm infants.

AIM: There is a discrepancy between the amount of transitional milk produced by mothers of preterm infants and the low capacity of premature infants to consume it. This milk can be used in milk banks, but previous studies found that there are large variations in the level of host-defence proteins in individual samples of milk from mothers of premature infants, which implies that large individual variations in antioxidative defence composition are also possible. METHODS: Milk samples were collected from 20 healthy mothers of preterm infants. We determined the values for non-enzymatic antioxidative capacity parameters (oxygen radical absorbance capacity (ORAC)), static oxidation-reduction potential (ORP), activities of antioxidant defence enzymes and the amount of vitamin C in whole milk, skim and whey fractions of transitional milk. RESULTS: The main low-molecular-weight antioxidant in transitional milk is vitamin C and most of it is contained in whey. ORAC is higher in whole transitional milk than in skim milk and whey, and ORP is lower in whole transitional milk than that in skim milk and whey. Antioxidative enzyme activities are similar in all individual samples of transitional milk from mothers of preterm infants. CONCLUSIONS: Our results indicate that transitional milk of mothers of preterm infants shows slow individual variations in antioxidative defence composition; therefore, it can be used in human milk banks.

Apple pectin-derived oligosaccharides produce carbon dioxide radical anion in Fenton reaction and prevent growth of Escherichia coli and Staphylococcus aureus.

Pectin is the main soluble fiber in apples or citruses. It may be fermented by gut microbiota to metabolites showing local intestinal and systemic effects. A wide range of beneficial effects of dietary pectin includes impacts on the redox milieu and microbiota profile. We prepared pectin-derived oligosaccharides (apple (APDO) and citrus) and polygalacturonic acid-derived oligosaccharides, using alkaline hydrolysis by hydrogen peroxide, and analyzed them by Fourier Transform Infrared spectrometry. Furthermore, we analyzed the effects of pectin-derived oligosaccharides on hydroxyl radical (HO)-generating Fenton reaction using electron paramagnetic resonance spin-trapping spectroscopy, and the effects on the growth of Escherichia coli and Staphylococcus aureus in the presence of dietary-relevant HO-generating system (iron+ascorbate). The oligosaccharides react with HO radical to produce carbon dioxide radical anion (CO2-). A comparative analysis showed that APDO has the most prominent bacteriostatic effect. This might be at least partially related to the higher capacity of APDO to produce CO2-, which specifically targets proteins and appears to have a longer lifetime and larger diffusion radius in biological systems compared to HO.

Determination of Microelements in Human Milk and Infant Formula Without Digestion by ICP-OES.

The concentrations of zinc (Zn), iron (Fe) and copper (Cu) in both human milk and infant formula were determined using a new sample preparation method, by inductively coupled plasma - optical emission spectometry (ICP-OES) and flame atomic absorption spectrometry (FAAS). Human milk samples were diluted in ultrapure water. The infant formula of powder samples (suitable for an infant 1-6 months of age) and standard reference material (SRM-1849) were analyzed in parallel. The results have shown that FAAS method was more sensitive for Fe determination in human milk while ICP-OES was more sensitive for both Zn and Cu detection. The limit of quantification for both Zn and Cu was 5 µg L-1 and 10 µg L-1 for Fe and the recovery for Zn, Fe and Cu was ranged from 90% to 94%, 97% to 103% and 90% to 102%, respectively. Mean concentrations of Zn, Fe, and Cu in human milk samples were 5.35, 0.47 and 0.83 mg L-1, respectively while these values in infant formula were ranged from 3.52-4.75 mg L-1, 3.37-4.56 mg L-1 and 0.28-0.41 mg L-1, respectively. Despite the sample complexity, the proposed method using dilution of milk samples with water was simple, rapid, effective and accurate. ICP-OES was a better method for Zn determination while FAAS was a better method for Fe determination. In the case of Cu both methods were comparable.

Zinc concentrations in human milk and infant serum during the first six months of lactation.

Normal supply of zinc to the newborn via milk is essential for normal development. Using ICP-OES, we analyzed changes in the level of Zn in milk and infant serum in the neonatal period (Day 1 and Day 28 post partum) and at 6 months after delivery, in the cohort of 60 mothers and exclusively breastfed babies. Zn level in the serum showed increase (significant at 6 months) during this period (mg/mL): Day 1: 0.52±0.12; Day 28: 0.59±0.19; 6 months: 0.68±0.28. The concentration of Zn in the milk showed an opposite (decreasing) trend during the follow up: Day 1: 4.70±1.74mg/L; Day 28: 2.65±1.06; 6 months: 0.46±0.36. A significant negative correlation was established between serum and milk [Zn] at day 28 (R=-0.338; p=0.008), whereas a positive correlation was found at 6 months between these parameters (R=0.306; p=0.018). There was no significant correlation between [Zn] in the milk and serum and infants' body mass, mothers' age and mass at delivery. The level of Zn in the milk at 6 months of lactation is not sufficient to meet the recommended values. This implies that in Serbian population, Zn supplementation might be needed in the later phase of lactation.

Antioxidative Activity of Colostrum and Human Milk: Effects of Pasteurization and Storage.

OBJECTIVES: Milk banks collect, pasteurize, and freeze/store human milk. The processing may alter redox properties of milk, but the effects have not been fully examined. METHODS: We collected 10 mature milk and 10 colostrum samples and applied a battery of biochemical assays and electron paramagnetic resonance spectroscopy to inspect changes that milk undergoes with pasteurization and 30 days storage at -20°C. RESULTS: Pasteurization and storage of raw milk did not affect total nonenzymatic antioxidative capacity, but specific components and features were altered. Urate radical and ascorbyl radical emerge as products of exposure of milk to hydroxyl radical-generating system. Processing shifted the load of antioxidative activity from ascorbate to urate and lowered the capacity of milk to diminish hydroxyl radical. Pasteurization caused a significant drop in the activity of 2 major antioxidative enzymes-superoxide dismutase and glutathione peroxidase, whereas freezing/storage of raw milk affected only superoxide dismutase. Colostrum showed drastically higher total nonenzymatic antioxidative capacity, hydroxyl radical scavenging ability, and glutathione reductase activity compared with mature milk. CONCLUSIONS: Pasteurization and storage affect nonenzymatic and enzymatic antioxidative agents in human milk. It appears that nonenzymatic antioxidative systems in colostrum and milk are different. The effects of processing may be partially compensated by fortification/spiking with ascorbate before use.

Reactions of superoxide dismutases with HS(-)/H2S and superoxide radical anion: An in vitro EPR study.

Interactions of hydrogen sulfide (HS(-)/H2S), a reducing signaling species, with superoxide dimutases (SOD) are poorly understood. We applied low-T EPR spectroscopy to examine the effects of HS(-)/H2S and superoxide radical anion O2.- on metallocenters of FeSOD, MnSOD, and CuZnSOD. HS(-)/H2S did not affect FeSOD, whereas active centers of MnSOD and CuZnSOD were open to this agent. Cu(2+) was reduced to Cu(1+), while manganese appears to be released from MnSOD active center. Untreated and O2.- treated FeSOD and MnSOD predominantly show 5 d-electron systems, i.e. Fe(3+) and Mn(2+). Our study provides new details on the mechanisms of (patho)physiological effects of HS(-)/H2S.

Dose-dependent survival of K562 cells subjected to irradiation, time course of endogenous enzyme activity and protective effect of applied superoxide dismutase.

PURPOSE: Irradiation-generated reactive species are proven to affect the cell survival and antioxidant enzyme levels. Radioresistance is a phenomenon which includes many cell mechanisms and signaling pathways. Superoxide dismutase (SOD) acts in and outside of cells after irradiation. The aim of this study was to determine LD50 (lethal dose for 50% of K562 cells), to monitor the effect of a chosen dose and exogenously applied superoxide dismutase (ExSOD) on the cell number and the activity of SOD, glutathione peroxidase (GSH-Px) and catalase (CAT). METHODS: The survival of irradiated (20-32.5 Gy) K562 cells was determined using the trypan-blue exclusion. Besides irradiated and non-irradiated cells (controls), another two groups of cells were treated with SOD (10-6 M) which then served as SOD-treated controls or were irradiated (30 Gy) one hour later. The number of cells and the activity of SOD, GSH-Px and CAT (using kinetic methods) were monitored after 1, 24, 48, 72 and 96 hrs in unirradiated, irradiated, SOD-treated and SOD-treated/irradiated experimental groups. RESULTS: K562 cells showed dose-dependent survival in the chosen range of doses. A dose of 30 Gy induced 50% cell mortality and increased the activity of all three investigated enzymes after 24 hrs. Pretreatment with SOD preserved the survival of irradiated cells and increased SOD, GSH-Px and CAT activity. ExSOD induced an increase of the activity of all examined enzymes. CONCLUSION: A balanced enhancement in endogenous antioxidative activity may be the cause of the increased radioresistance of K562 SOD-pretreated cells.

Redox therapy in neonatal sepsis: reasons, targets, strategy, and agents.

Neonatal sepsis is one of the most fulminating conditions in neonatal intensive care units. Antipathogen and supportive care are administered routinely, but do not deliver satisfactory results. In addition, the efforts to treat neonatal sepsis with anti-inflammatory agents have generally shown to be futile. The accumulating data imply that intracellular redox changes intertwined into neonatal sepsis redox cycle represent the main cause of dysfunction of mitochondria and cells in neonatal sepsis. Our aim here is to support the new philosophy in neonatal sepsis treatment, which involves the integration of mechanisms that are responsible for cellular dysfunction and organ failure, the recognition of the most important targets, and the selection of safe agents that can stop the neonatal sepsis redox cycle by hitting the hot spots. Redox-active agents that could be beneficial for neonatal sepsis treatment according to these criteria include lactoferrin, interleukin 10, zinc and selenium supplements, ibuprofen, edaravone, and pentoxifylline.

Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant mesial temporal lobe epilepsy.

An altered metal and electrolyte profile has been implicated in the pathologic mechanisms of chronic epilepsy; however, no study has comprehensively measured hippocampal concentrations of these elements in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (mTLE-HS). We therefore analyzed hippocampi of 24 patients with drug-resistant mTLE-HS (mean age 35.6 ± 9.4 years) who underwent anterior temporal lobe resection and amygdalohippocampectomy and 17 hippocampi obtained by autopsy from 13 controls (mean age 40.5 ± 12.9 years), using inductively coupled plasma optical emission spectrometry (ICP-OES). Epileptic hippocampi showed significantly lower concentrations (µg/g of tissue) of copper (HS: 2.34 ± 0.12; control [C]: 3.57 ± 0.33; p < 0.001), manganese (HS: 0.205 ± 0.030; C: 0.409 ± 0.064; p = 0.004), and potassium (HS: 2,001 ± 59; C: 2,322 ± 61; p < 0.001), and increased sodium levels (HS: 1,131 ± 22; C: 1,040 ± 25; p = 0.010). Zinc, iron, calcium, and magnesium levels did not differ in HS and controls. In summary, copper and manganese levels are deficient, whereas iron level is unchanged in hippocampi from patients with mTLE-HS. Our results provide a basis for understanding the potential involvement of different metals and electrolytes in the pathology of HS.

Antioxidative system in the erythrocytes of preterm neonates with sepsis: the effects of vitamin E supplementation.

BACKGROUND: Vitamin E is routinely supplemented to preterm babies, including those with neonatal sepsis. Our aim was to examine the effects of neonatal sepsis and vitamin E on antioxidative system (AOS) in the blood. METHODS: A prospective, randomized, open label study involved 65 preterm neonates (control/sepsis - 34/31), which were divided into two subgroups - non-supplemented and supplemented with vitamin E (25 IU/day for 60 days). The activities of superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were determined in erythrocytes at days 0, 30, and 60, following sepsis diagnosis. RESULTS: There was no difference in the activity of AOS between controls and neonates with ongoing sepsis. At 60 days, septic neonates showed higher CAT activity compared to controls (P = 0.027), and lower GPx activity compared to 0 days (P = 0.022). The later was mitigated by vitamin E, which on the other hand provoked lower GPx activity at 30 days, compared to untreated septic neonates (P = 0.014). In addition, vitamin E suppressed GR activity in septic neonates (P = 0.025 and P = 0.017 at 30 and 60 days). Finally, vitamin E supplementation in control neonates provoked a significant increase of GPx activity (P = 0.015 at 60 days). CONCLUSIONS: The absence of altered redox settings in the blood of neonates during sepsis episode, and vitamin E-provoked decrease in the activity of some components of AOS, suggest that the supplementation of vitamin E in these patients might not be rational.